Isotope ratio mass spectrometry as a tool for source inference in forensic science: A critical review

Forensic Science International 251 (2015) 139–158

Contents lists available at ScienceDirect

Forensic Science International journal homepage: www.elsevier.com/locate/forsciint

Review Article

Isotope ratio mass spectrometry as a tool for source inference in forensic science: A critical review Natacha Gentile a,*, Rolf T.W. Siegwolf b, Pierre Esseiva a, Sean Doyle c, Kurt Zollinger d, Olivier Dele´mont a a

Ecole des Sciences Criminelles, Universite´ de Lausanne, Batochime, 1015 Lausanne-Dorigny, Switzerland Laboratory of Atmospheric Chemistry, Paul Scherrer Institut, 5232 Villigen, Switzerland Linked Forensic Consultants Ltd, Raumati Beach 5255, Wellington, New Zealand d Forensic Science Institute Zurich, 8004 Zurich, Switzerland b c

A R T I C L E I N F O

A B S T R A C T

Article history: Received 15 December 2014 Received in revised form 17 March 2015 Accepted 31 March 2015 Available online 9 April 2015

Isotope ratio mass spectrometry (IRMS) has been used in numerous fields of forensic science in a source inference perspective. This review compiles the studies published on the application of isotope ratio mass spectrometry (IRMS) to the traditional fields of forensic science so far. It completes the review of Benson et al. [1] and synthesises the extent of knowledge already gathered in the following fields: illicit drugs, flammable liquids, human provenancing, microtraces, explosives and other specific materials (packaging tapes, safety matches, plastics, etc.). For each field, a discussion assesses the state of science and highlights the relevance of the information in a forensic context. Through the different discussions which mark out the review, the potential and limitations of IRMS, as well as the needs and challenges of future studies are emphasized. The paper elicits the various dimensions of the source which can be obtained from the isotope information and demonstrates the transversal nature of IRMS as a tool for source inference. ß 2015 Elsevier Ireland Ltd. All rights reserved.

Keywords: Isotope ratio mass spectrometry IRMS Forensic Stable isotope Source inference Discrimination

Contents 1. 2.

3.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The notion of source inference. . . . . . . . . . . . . . . . . . . . . . . . . 1.1. Application of IRMS to fields not directly related to police services . Authentication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Environmental issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Fight against doping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Application of IRMS to the traditional fields of forensic science . . . . Illicit drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Natural illicit drugs . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1.1. Synthetic illicit drugs . . . . . . . . . . . . . . . . . . . . . . . . 3.1.2. Human provenancing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Human provenancing: in essence . . . . . . . . . . . . . . . 3.2.1. Ignitable liquids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Ignitable liquids: in essence . . . . . . . . . . . . . . . . . . . 3.3.1. Explosives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4. Preblast studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.1. Postblast studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.2. Explosives: in essence . . . . . . . . . . . . . . . . . . . . . . . . 3.4.3.

* Corresponding author. Tel.: +41 216924646; fax: +41 216924605. E-mail address: [email protected] (N. Gentile). http://dx.doi.org/10.1016/j.forsciint.2015.03.031 0379-0738/ß 2015 Elsevier Ireland Ltd. All rights reserved.

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . . . . . . .

140 140 140 140 140 141 141 141 141 144 147 148 148 148 148 149 151 151

140

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

3.5.

4.

Other applications. . . . . . . . Paints . . . . . . . . . . 3.5.1. Soils . . . . . . . . . . . 3.5.2. Fibers . . . . . . . . . . 3.5.3. Tapes . . . . . . . . . . 3.5.4. Plastic. . . . . . . . . . 3.5.5. Safety matches. . . 3.5.6. Microbial studies . 3.5.7. 3.5.8. Documents . . . . . . Poisons . . . . . . . . . 3.5.9. 3.5.10. Miscellaneous . . . Conclusion . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

1. Introduction The applications of IRMS in forensic science were reviewed for the first time by Benson et al. in a concise paper presenting the theory, instrumentation and forensic applications up to 2006 [1]. Few years later, Meier-Augenstein published an overview of the theory and principles underlying stable isotopes in addition to details on technical aspects and general considerations for the forensic application of IRMS. He also surveyed different forensic applications illustrated by the main ongoing research in the fields and some case studies [2–4]. Some of the main applications were presented by Chesson et al., from the point of view of isotope geochemists [5]. The applications of IRMS in forensic science are numerous and varied. The flourishing contributions of the researchers have led to a huge quantity of information. This paper provides a global overview on the potential and limits of IRMS through a systematic and thorough review of the studies undertaken in the traditional fields of forensic science (the term ‘traditional’ is to be understood here as ‘generally dealt with by the police’). Publications on illicit drugs, flammable liquids, human provenancing, explosives and miscellaneous applications (such as paints, soils, fibers, packaging tapes, safety matches, plastic and paper, etc.) are reviewed and the essential detail is extracted from the study to assess the state of application of IRMS. For each field, the main findings are summarised in a discussion, where the relevance of the results is brought to light in a forensic context. The discussions point at the needs and challenges of future research. The notion of source inference is first introduced. The first part reports applications of IRMS to fields which are not directly related to police services. In the second part, studies undertaken in the traditional fields of forensic science are reviewed. The ability of IRMS to answer the different questions related to the notion of source is revealed throughout the review. 1.1. The notion of source inference The applications of IRMS in forensic science all have a common approach: the exploitation of stable isotopes in order to infer the source of a trace. This aspect is often at the heart of the questions to be answered in forensic science. The notion of source in itself is vast and goes far beyond the scope of this article. Interested readers are referred to the work of Kwan for further considerations [6]. The variety of information obtained in the applications of IRMS demonstrates the ability of this technology to treat the questions of source under different aspects. Indeed, the notion of source does not cover only one single question but a variety of questions, which reflect its numerous dimensions and are dependant on the trace and its context. Its applications in several fields which are not directly related to police services – although directly in connection

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

. . . . . . . . . . . . .

152 152 152 152 152 153 153 153 153 153 153 153 154

with law – highlight the transversality and potential of IRMS to answer the many questions of the source.

2. Application of IRMS to fields not directly related to police services 2.1. Authentication A major application of IRMS is authentication, as employed in food, pharmaceuticals and fields concerned with forgery (luxury product, watches, etc.). This technology allows inferring the authenticity, forgery or adulteration of a material. More precisely, the authenticity of a material – and thus its source – may be defined by its geographical provenance (regional or continental) or its specific signature derived from features of production (manufacturer, batch, raw materials, production method, etc.). Several authors reviewed the numerous studies undertaken in food authentication [7–12]. Most of the studies concern the assignment of the geographical origin of food and the detection of adulterated products. The distribution of stable isotopes in both organic and inorganic materials are characteristic of geographical or regional locations. Isotopic analyses of light elements, mostly hydrogen and oxygen, indicators of climatic characteristics, are often supplemented by heavier trace element isotope analysis, the most common being strontium [9,11]. Authentication of animal derived products is based on knowledge of food chain. Their geographical provenance may be inferred, as animal tissues and products necessarily inherit their isotopic signature from the isotopic composition of their diet (food and water intake) [7,13,14]. Beside the geographical source, stable isotope analysis has also helped in answering the question of the production method of food (organically grown food vs. grown with synthetic fertilisers, specific animal diets, etc.) [10,12]. Although less popular than food authentication, authentication of pharmaceuticals with stable isotopes has also been evaluated. Individual batches of active pharmaceutical ingredients analysed by IRMS are characterised by specific isotopic signatures [15]. The combination of stable isotope ratios allows differentiating genuine from counterfeit pharmaceutical tablets [16]. 2.2. Environmental issues The application of IRMS in environmental issues, such as wildlife forensic science or contamination studies, shows the potential of isotope information to answer different questions of the source. In wildlife forensic science, the food and water intake reflected in animal tissues is used to gain information on the movements of animals [17–25]. The turnover rate of the tissue (feather, hair, muscle, etc.) provides a time frame, ranging from weeks to months or years, for the interpretation of isotope ratios.

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

The migration patterns can help in taking actions to protect endangered species (prevention against poaching) or in better understanding particular animals. Mostly d13 C, d15 N, d34 S accompanied by d87 Sr, are analysed to infer the origin of animals. d18 O, and especially d2 H, may provide further geographical information at continental scale [26]. The use of IRMS in environmental contamination studies is often undertaken either in a risk prevention perspective or to determine the liable party. Stable isotope ratios measurements have been exploited to trace the source of contaminants or to differentiate sources of chemicals [27–32]. The notion of source in contaminant studies is complex as it depends on the context. It may be the entity producing, transporting, loading, diffusing, spilling or dumping the contaminants (site, manufacture [33], ship, etc.), the type (e.g., pyrogenic vs. petrogenic), the geographical provenance, etc. Most studies reported on the d13 C analysis, although other elements such as hydrogen, nitrogen, oxygen, chlorine or sulphur were progressively reported in publications to trace sources of contaminants or to evaluate their fate in environment (potential risk for health) [34–37]. Other research focused on the identification of degradation reactions, as well as non-degradative processes, such as volatilisation or dilution which may induce isotope fractionation [27,28,35,37–43]. The knowledge in this field has been reviewed by two comprehensive papers [44,45]. 2.3. Fight against doping The ability of GC-C-IRMS (gas chromatography combustion isotope ratio mass spectrometry) technology to distinguish between endogenous and exogenous (synthetic) testosterone and its metabolites was reported for the first time in 1994 [46]. Since then, literature on carbon isotope ratio measurements of urinary steroids has expanded and the technology has become the method of choice in the fight against doping by inferring the biological or synthetic source of steroids [47–54]. As the results may be presented in court, as in the case of Floyd Landis v. USADA [55], various studies involving different reference populations and evaluating the influence of factors, such as diet or gender on the d13 C value were undertaken. A comprehensive review by Piper et al. sets the extent of knowledge [56]. 3. Application of IRMS to the traditional fields of forensic science The following subsections report the results obtained by the different groups of researchers. Readers are referred to tables, where provided, indicating the range of values1 measured in the studies. All reported d values are expressed in % relative to Vienna Pee Dee Belemnite (VPDB) for carbon, atmospheric air for nitrogen, and Vienna Standard Mean Ocean Water (VSMOW) for oxygen and hydrogen. Likewise, values have been reported without their standard deviation, as they are provided as an indication for the review. Although the results of the studies are briefly presented in this paper, a detailed review of the published articles can be found in [57]. 3.1. Illicit drugs 3.1.1. Natural illicit drugs Most studies focusing on natural illicit drugs are based on the postulate that stable isotope ratios distribution in plant materials reflects the environment in which the plant grows (climatic conditions such as humidity, temperature, amount of light, 1

d values are reported as mentioned in the studies, without rounding numbers.

141

ambient carbon dioxide, etc.) and its metabolic factors. On this theoretical basis, isotope ratios may therefore be useful indicators of the geographical origin of specimens of natural illicit drugs. 3.1.1.1. Cannabis. Isotope ratio mass spectrometry was applied to cannabis for the first time in 1979 by Liu et al. [58]. Most of the studies focused on the differentiatiation of cannabis coming from different geographical locations based on the bulk d13 C and d15 N values of cannabis [58–63], more rarely with additional data on d2 H [64,65] and d18 O [64]. The specimens, coming from seizures made by law enforcement, were of known geographical origin. Data have been collected on cannabis grown in the United States of America (USA) [58,63–65], South America [60,63], Russia and Ukraine [59]. An interesting feature of the inference of the geographical source of cannabis is the use of the information to collect knowledge on the dimension of the traffic. The comparison of specimens of unknown origin with samples of known geographical location can provide information on whether the seized cannabis was produced locally or not [60,64,66]. Furthermore, in some cases, it can also suggest the existence of traffic routes [61]. The d13 C values are reported to oscillate on a narrower range than d15 N values, more important variations in d13 C [63,64] have also been reported. Isotopic variations measured in cannabis concerned different parts of the plants. Leaf material [58–60,63– 65,67] was the most common type of material analysed, followed by inflorescence [58,63,67]. Shibuya et al. evaluated the variability of the isotopic profile obtained from seeds, twigs, leaves and from the whole specimen and observed no significant difference [60]. On the contrary, West et al. noted significant differences between the inflorescence and leaves of outdoor grown plants for d13 C and d15 N (0.6% and 1.1%, respectively) [63]. Fundamental data on cannabis isotopic intravariability were published by Denton et al. [67]. Sampling lower, middle and upper leaves of plants coming from 3 crops, they measured within-plant variations of up to 1–2% for d13 C and more than 1% for d15 N. Similarly, variations of up to 2.1% for d13 C and 6.7 % for d15 N were noticed within a crop. In the same way, significant variability within specimens was noticed for d18 O (up to 11 %) and d2 H (up to 40%) [64]. The relationship between d13 C and d15 N values of cannabis plants and their environmental and growth conditions (indoor/outdoor, watering and fertiliser) was also examined by Denton et al. [67]. Significant differences in d13 C values were observed between specimens from indoor and outdoor grown cannabis plants. Under controlled environment experiments, watering was observed to have a significant impact on the d13 C and d15 N values. Furthermore, the d15 N value of cannabis plant could be related to the type of fertiliser used (industrial fertiliser versus animal manure). West et al. also reported that stable isotope ratios indicated cultivation methods rather than regional differences [63]. Based on theoretical fractionation models of plants, West et al. proposed an interpretation framework with d13 C and d15 N thresholds to categorise seized specimens of cannabis (indoor/outdoor; organic/inorganic fertiliser) [63]. The performance of the model was good, as most specimens of known growth environment fell within the corresponding area. This framework was also used by Booth et al. on their dataset to categorise their specimens [64]. In a different way, Shibuya et al. also noticed the influence of environmental conditions on the isotopic profile [60]. Different ranges of d13 C and d15 N values were observed between specimens grown in dry, humid and semi-humid regions. While all the studies used EA-IRMS (elemental analysis isotope ratio mass spectrometry), Muccio et al. compared the bulk stable isotope data and the specific d13 C value of D-9-tetrahydrocannabinol (THC), cannabinol (CBN) and cannabidiol (CBD) of specimens obtained by GC-C-IRMS [68].

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

142

In 1979, Liu et al. already suggested that the use of other analytical methods in combination with IRMS could increase the discrimination power [58]. Shibuya et al. used stable isotope data in addition to inorganic constituents measured by high resolution inductively coupled plasma mass spectrometry (HR-ICP-MS) to verify existing differences between specimens of cannabis grown in different regions of Brazil [62]. West et al. complemented their research on the inference of the geographical source of cannabis by analysing strontium isotope by thermal ionisation mass spectrometry. The use of the isotopic profile of cannabis in a casework was reported by the FIRMS network (Forensic Isotope Ratio Mass Spectrometry network Ltd.). In a case opposing R v. Thomas Ivan Brettschneider, the d13 C and d15 N values of cannabis seized from a truck and cannabis from a plantation, which could not be differentiated at 95% level confidence, were used as evidence in the Supreme Court of the Northern territory in the 1980’s [69]. Table 1 summarises the details of the studies on the analysis of cannabis. 3.1.1.2. Cocaine. The studies on cocaine all refer to the geogaphical source of cocaine specimens or coca leaves [59,70–72]. While the d13 C values oscillated on a narrow range, a wider span of d15 N values was measured [70,72–74]. d2 H values were reported to offer additional discrimination [74]. Most studies on the analysis of cocaine specimens reported on the bulk d13 C and d15 N values. Progressively, the specific carbon and nitrogen isotope ratios of cocaine were also measured by GC-C-IRMS [59,74,75]. Besides, Muccio et al. emphasized the usefulness of combined detectors for the identification of the compounds [75]. In order to understand the origin of isotopic variations, the effect of the manufacturing process of cocaine on the isotopic profile was investigated [76]. Using different Colombian, Peruvian and Bolivian conversion methods, the processing of cocaine base to cocaine hydrochloride (HCl) in controlled settings did not significantly affect the d13 C value. However, the d15 N value showed a positive shift ranging (from 0.8 to 3.7%) related to the precipitated fraction of cocaine. Casale et al. demonstrated the progressive depleted values of successive cocaine HCl precipitates for reactions with less than 100% yield. Sewenig et al. studied the carbon and nitrogen isotope variations of cocaine bricks of a 1.2 ton seizure [72]. This allowed for the first time gathering knowledge on the isotopic variations in cocaine bricks on a large scale. The d13 C variations were assumed to be related to different humidity conditions. The d15 N values around 5% were attributed to growth conditions, in particular soil, fertiliser and land-use history,

Table 1 Summary of data on the bulk isotopic analysis of cannabis in literature.

*

while the very depleted d15 N values were interpreted as the result of successive precipitations of cocaine HCl. The isotopic profile has been combined with the alkaloid content of coca leaves to infer their country of origin [71] and to the physical characteristics (imprinted logo) of cocaine bricks to confirm links between specimens [72]. Table 2 summarises the range of isotopic values of cocaine reported in the different studies. 3.1.1.3. Heroin. As for cocaine, the inference of the geographical source of heroin specimens is the aim of the majority of the studies [59,70,77–80]. Specimens of heroin coming from different regions, mostly Southeast and Southwest Asia, Colombia and Mexico, can be differentiated based on their d13 C and d15 N values. However, because the d13 C value of heroin depends on the geographical origin of the opium poppy, as well as on the source of the acetic anhydride used to convert morphine to diacetylmorphine, the inference of the geographical source of a specimen of heroin only based on its d13 C value may be inaccurate [81]. Nevertheless, the deacetylation of heroin allows recovering the original d13 C value of morphine, its natural precursor. As the d13 C value of morphine reflects the environmental conditions of growth of the opium poppy, it could provide an indication on the geographical origin of the specimens of heroin [70,76,79,81]. The combination of the d13 C values of both heroin and its extracted morphine may provide information on the acetylating reagent [79]. The isotopic effect of heroin deacetylation and morphine acetylation by acetic anhydride [76,81] on the d13 C value of the resulting product, respectively morphine and diacteylmorphine, was investigated. The production of heroin base from the acetylation of morphine induced an isotopic fractionation ( 3.3% in [81], 1.5% in [76]). This difference in shift suggests there might be a scale factor, as Besacier et al. worked on milligrams and Casale et al. on kilograms. Furthermore, while the conversion of heroin base to its HCl salt form did not induce a carbon isotopic fractionation, it led to variable isotopic depletions of the d15 N value [76]. Significant depleted d15 N values were reported to result from the successive precipitation of heroin base into heroin HCl. Bulk and compound specific isotope analysis were used for discrimination. The studies using GC-C-IRMS generally focused on the specific determination of the d13 C value of diacetylmorphine [74,77,81,79,80,78,82,83,59], morphine [59,80] or acetylcodeine [83]. Besacier et al. used GC-C-IRMS to supplement the analytical procedure of their heroin specimens (i.e. qualitative, quantitative and trace impurities analysis) [83]. The d13 C results confirmed the groups obtained on the major and minor constituents of the

indicates d values estimated from graphs.

d13 C (%)

d15 N (%)

d18 O (%)

d2 H (%)

34.15 to 27.82 36.4 to 25.0

– 1.0 to +15.8

– –

– –

28.38 to 26.43 32 to 23 32 to 24 30 to 26*

3.17 to +9.65 4 to +10 4 to +11 0 to +8*

– – – –

– – – –

–

–

Study

Material analysed

Number specimens

Origin

Liu et al. [58] Denton et al. [67]

Leaves flowers Leaves

6 150

Galimov [59] Shibuya et al. [60]* Shibuya et al. [61]

Leaves Whole plant Whole plant

West et al. [63]

Leaves flowers

8 90 50 104 76 508 3 2 41 56 122 764 5

USA Australia, Papua, Thailand Russia, Ukraine Brazil Brazil Unknown USA Colombia Mexico Unknown Alaska Unknown North America Unknown

51.8 to

Booth et al. [64]

Leaves

Hurley et al. [65] Muccio et al. [68]

Leaves Unknown

20.3

53.8 to 26.4 61.8 to 24.6 35.1 to 28.2 32.45 to 27.168

7.9 to +29.5

12.5 to +12.1 5.0 to +14.7 – –

+10.4 to +37.0 +10.0 to +34.5 – –

203.1 to 136.7 214.6 to 107.5 160 to 125 –

N. Gentile et al. / Forensic Science International 251 (2015) 139–158 Table 2 Ranges of isotopic values of cocaine reported in literature. Method

Study *

Finnigan [73] Ihle and Schmidt [74]

*

143

indicates d values estimated from plots or graphs. Number specimens

d13 C (%)

Origin

d15 N (%)

6 4

Unknown Unknown

35.5 to 34.4 to

33.5 33.6

13 to 5 13.7 to 5.4

Ehleringer et al. [70]*

EA-IRMS EA-IRMS GC-C-IRMS EA-IRMS

28

34.8 to

33.5

13 to

Casale et al. [76] Galimov et al. [59]

EA-IRMS EA-IRMS

10 15

Bolivia Peru Ecuador Colombia Peru Colombia

Sewenig et al. [72] Muccio and Jackson [75]*

GC-C-IRMS EA-IRMS GC-C-IRMS

132 6

Unknown Commercial

4

34.8 to 34.4 39.92 to 30.85

10.3 to 6.6 10.36 to 2.19

37.31 to 34.54 35.4 to 33.9 37 to 35

10.50 to 1.64 17.4 to 1.8 –

Standards Unknown

Table 3 Summary of isotopic studies on the analysis of heroin reported in literature.

Study

Method

Number specimens

Origin

Desage et al. [77]

GC-C-IRMS

Unknown

Finnigan [73]* Dautraix et al. [82] Ihle et al. [74]

4 1 5

Besacier et al. [83] Besacier et al. [81]

EA-IRMS GC-C-IRMS EA-IRMS GC-C-IRMS GC-C-IRMS GC-C-IRMS

Turkey, India, Niger, Pakistan, Thailand Unknown Unknown Unknown

Besacier et al. [84]

EA-IRMS

20

Ehleringer et al. [70]*

EA-IRMS

76

Carter et al. [86] Casale et al. [76] Galimov et al. [59]

EA-IRMS EA-IRMS EA-IRMS

5 12 3

GC-C-IRMS EA-IRMS GC-C-IRMS GC-C-IRMS EA-IRMS GC-C-IRMS EA-IRMS

6 14

Unknown

10 20

unknown Unknown

Unknown

Unknown

Idoine et al. [78]* Zhang et al. [79] Casale et al. [80] Meier-Augenstein et al. [4] a

9 31

*

indicates d values estimated from plots.

Unknown India, Africa, Lebanon, Turkey, Syria, Thailand, Pakistan India, Turkey, Lebanon, Thailand Mexico, S-E Asia, S-W Asia, South America Unknown Colombia Colombia, Korea, Afghanistan

d13 C %

d15 N %

d18 O %

d2 H %

–

–

–

– –

– –

– –

– –

4.34 to +0.40

–

–

2 to +3

–

–

33.4 to 31.9 32.4 to 27.5 35.11 to 33.26

8.3 to 3.0 12.2 to +4.8a 6.69 to +1.29

+18.3 to +19.7 – –

– –

38.35 to 32.74 34 to 29 40.71 to 32.60 37.51 to 35.23 32.8 32.3

2.93 to +7.15 9.0 to 2.5

+15 to +20

2.5 to

– –

33.561 to

33 to 32.81

31.568

31

9 to

1

– 3.6 to +1.7

34.1 to 31.4 34.97 to 31.16 34.97 to 28.06

– –

– 34 to

–

29

– – –

0.5

+11.5 to +32.1

173.6 to

143.5

200 to 203 to

110 158

179 to

80

– –

Heroin base and HCl precipitates were considered.

specimens. Similarly, the rare alkaloid profile of some heroin specimens was complemented with their bulk isotopic profile in order to see if the values could correspond to specimens of known geographical origin [80]. Dautraix et al. reported on the constant and reproducible carbon isotopic fractionation of paracetamol when mixed with heroin. Besacier et al. exposed their interest in the isotopic profile of cafeine used as cutting agent, by analysing the specific d15 N values of diacetylmorphine and caffeine in heroin specimens [84]. The potential of isotopic information to trace cutting agents added at each stage of the distribution chain was mentioned. In a similar way, Galimov et al. indicated that the specific d13 C value of caffeine suggested different cutting events [59]. The isotopic profile of heroin is mentioned to have been used in two caseworks. In a casework referred in [85], the isotopic profile

of heroin traces recovered in a vehicle was compared to that of a bulk seizure. As their isotopic profiles were different, it was concluded that the trace did not originate from the bulk material. Carter et al. combined heroin purity with the chemical profile, the isotopic composition of heroin and of the cling film wrapping the specimens to express a conclusion on the supply of heroin, the cutting and packaging [86]. Table 3 summarises the range of bulk and compound specific2 isotopic values of heroin reported in literature. 3.1.1.4. Natural illicit drugs: in essence. Most studies on the isotopic analysis of natural illicit drugs have focused on the determination 2 When GC-C-IRMS was used, the values reported in the table are for diacetylmorphine.

144

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

of the geographical origin of the specimens. The bulk d13 C and d15 N values are the most common parameters measured by IRMS for cannabis, cocaine and heroin. Growing interest is now focused on d18 O and d2 H values. As they are related to precipitation and humidity, they may offer new possibilities to assist in differentiating the geographical origin of plant-derived products. However, inference of the geographical source based on stable isotopes is not always evident. For cannabis, the distinction of geographical regions according to the natural d13 C and d15 N isotopic variations is hindered by the wide range of growth conditions of indoor and outdoor crops. Whereas the natural isotopic variations of outdoor grown cannabis are well documented, research on cannabis grown indoor is more limited. Indoor cultivation conditions often impose a set of unnatural conditions (hydroponic system, growing conditions, forced light cycles, over-ventilation, moist environment, optimum nutrients distribution, etc.), stressing the plant, in order to accelerate growth and increase the yield of the active substance. In contrast, outdoor crops, although hidden in the shade or among flora to prevent aerial identifications, reflect a more natural environment. As a result of these cultivation methods, carbon and nitrogen stable isotopes of seized cannabis specimens are not traceable to a geographic origin, but rather indicative of a growth environment as attested by the results of current studies. d13 C value may indicate indoor or outdoor growth, although there is an overlap between the two, preventing samples in the middle zone from a categorical classification. According to empirical data, outdoor cannabis plants displayed d13 C value between 32 and 23, whereas indoor plants showed values between -36 and 27%. Even more depleted values as much as 61.8% have been measured and have been attributed to presumed indoor grown plants [64], due to additional CO2 cylinder supply. Depending on the soil conditions and the biosynthetic mechanisms, nitrogen isotope ratio is related to the source of nitrogen of the plant, mainly influenced by the type of fertiliser used. Organic and inorganic fertilisers fed plants can be differentiated on their d15 N value. In addition, the d15 N variations between specimens indicate that many different inorganic fertilisers are used. Moreover, ongoing research on hydrogen stable isotope may provide additional elements for regional or geographic origin determination [65]. As indoor cultures (hydroponic/aeroponic) have largely supplanted outdoor crops in many countries to limit visibility and to increase marijuana yields, there is a tangible need for knowledge on the isotopic variability of indoor grown cannabis. Since cannabis plants reflects their growth environment, a relevant question in a case-to-case comparison pertains to the possibility to discriminate specimens grown under different sets of indoor conditions. Indeed, the isotopic variations of the different nutrients administered to plants (non-atmospheric CO2 from gas cylinders or fermentation CO2 generators, fertiliser and water supply) as well as the influence of conditions such as light exposure, humidity, temperature and ventilation conditions, may contribute to create an isotopic signature reflecting a given set of indoor growth conditions, differentiable from other sets of growth conditions. This is of course a hypothesis that needs to be investigated. In that perspective, additional data on intravariability are much needed. Some studies have shown that different parts of the cannabis plant exhibit different bulk isotopic profile. While no significant isotopic differences were noticed between leaves, twigs and seeds [60], variations of isotopic composition were observed between leaves and flowers [58,63]. Moreover, significant variations were observed within plant leaves. Light, ventilation and CO2 supply may affect within plant variability and result in isotopic stratification for dense crops. Finally, questions pertaining to the influence of the matureness (grow stage) of the plant and ageing of

the specimens (THC is degraded into CBN and CBD over time) on the isotopic profile should be investigated. For illicit drugs requiring chemical processing, research has shown that stable isotopes may be used to infer their geographical origin. Cocaine from different geographical growing regions exhibited differentiable isotopic profiles, suggesting that stable isotopes are connected to the geographical location of coca leaves. The influence of the chemical extraction of cocaine alkaloids and the conversion of cocaine paste to cocaine base is however unknown. Interestingly, as highlighted by Ehleringer et al. [70,71], the bulk d13 C and d15 N values of cocaine are significantly more depleted (-3 to -8 %) than the bulk plant material. The geographical origin of heroin may be revealed through the d13 C value of morphine, while the d13 C value of heroin provides information on the acetylating reagent. The study of Casale et al. provides possible explanations on the origin of the d15 N variations through the manufacturing process of heroin [76]. At present, it appears difficult to relate the nitrogen isotopic variations to a specific level of source. Moreover, most research analysed the bulk isotope values of illicit drugs. Natural minor and major compounds, as well as cutting agents such as phenacetin or lidocaine in cocaine, or paracetamol and caffeine in heroin, contribute to the bulk value, reflecting thus an average of the isotopic composition. An indisputable fact is that specimens from seizures have different isotopic profiles [72,86]. The origin of such variations is currently unknown and could remain so for a while. However, an exciting prospect is the comparison of the isotopic profile with the profile of the natural and production compounds, as both are connected to growth environment and chemical processing. The association and exploitation of different types of variables provide information on different levels of sources for investigative purpose. 3.1.2. Synthetic illicit drugs Unlike natural illicit drugs where IRMS technology may assist in ascertaining the geographical origin of the plant-derived product, isotopic variations in synthetic illicit drugs are expected to originate both from the precursors and reagents used and the synthetic reactions. The measurement of stable isotopes is therefore used in a source inference perspective to establish a link between a precursor and a synthetic illicit drug or between two seizures. It is also used to determine the synthetic pathway used to manufacture the illicit drug. 3.1.2.1. Ecstasy and MDMA. Most studies reported the analysis of 3,4-methylenedioxy-N-methylamphetamine (MDMA)-containing tablets by EA-IRMS, except for two studies in which the specific value of MDMA was measured by GC-C-IRMS [87,88]. The extraction of MDMA by supported liquid extraction cartridges, before the bulk analysis of pure MDMA was also reported [89]. The analysis of MDMA contained in seized ecstasy tablets showed limited d13 C variations in contrast to the d15 N values which covered a larger range [87,88,90,91]. While the d13 C values were observed to be close to that of precursors (safrole and isosafrole) [90,91], the large d15 N variations were presumed to originate from the synthetic route of the manufacturing process [88]. The experiments of Carter et al. and Palhol et al. confirmed that isotopic fractionation occurred during reactions [90–92]. The reverse conversion of MDMA into its reciprocal ketone and the synthesis of MDMA through reductive amination and Leuckart reaction showed the existence of isotopic differences between the starting materials and the final products. The inference of the synthetic route of MDMA and the employed precursors were investigated by Billault et al. and Buchanan et al. using bulk isotope analysis [93–95]. The synthesis of MDMA under controlled conditions with different nitrogen precursors showed that the

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

145

d13 C value was influenced by the number of steps of the synthesis and the d15 N value was dependent on the nitrogen precursor,

The isotopic values of MDMA reported in the different studies are summarised in Table 4.

synthetic pathway and reaction conditions [93]. However, distinct correlation patterns between the isotopic profile and the synthetic route could not be highlighted, because of the d15 N range of variations and lack of repeatable values for 4 steps-syntheses. This isotopic variability within a synthetic route was studied by Buchanan et al. [94,95]. While the first results suggested d2 H data could help in differentiating MDMA from different synthetic route [94], the second study on the modifications of the conditions of the Pt/H2 reductive amination synthesis revealed that significant isotopic variations were measured within 32 synthesised batches [95]. Despite careful controlled synthesis conditions, even stable isotopes supposed to remain unchanged and close to the value of the starting materials, such as d13 C and d18 O, were subject to isotopic fractionation. Indeed, isotope ratios were highly dependant on the reaction conditions and reaction efficiency. The authors stressed the complexity of the situation for the interpretation of isotopic data. The d15 N values of 106 tablets were combined with their physical charateristics (logo, mass, size, form, content, etc.). Applying principal component analysis (PCA) followed by hierarchical cluster analysis (HCA), the specimens were partitioned into 5 groups, most probably with similar synthetic pathway [96]. As in their previous studies [90,91], the established links were confirmed by the chemical profile of the tablets. Buchanan et al. combined isotopic data of synthesised samples with the organic impurities profile measured by GC–MS, in order to differentiate batches of MDMA or synthetic routes [97]. Despite the use of diverse data preprocessing and pattern recognition techniques, neither GC–MS impurities, nor IRMS data on their own allowed full discrimination of the synthetic route or batch of starting material. However, the application of discriminant analysis (DA) to the combined data set allowed discriminating MDMA samples coming from different synthetic routes. Only two case reports mention the use of isotopic data in real cases. Carter et al. reported the analysis of the isotopic composition of 2 seizures of ecstasy tablets found in the same place [86,98]. The d13 C and d15 N values of the selected tablets were found indistinguishable at 95% confidence. Considering their background study [88], the authors concluded that they originated from the same source [69]. Neumann, as cited in [99], reported the use of isotopic information as evidence in the Regional Superior Court judgement of a case concerning a large MDMA clandestine laboratory. The isotopic analysis of MDMA samples proved that at least 2 batches of MDMA had been produced by the laboratory.

3.1.2.2. Methamphetamine and precursors. The growing concern in public health on methamphetamine engendered several studies on that particular type of drugs. Several research studies focused on the analysis of methamphetamine synthesised from precursors, as well as on the analysis of the precursors themselves. Particular interest was taken in the identification of the manufacturing processes of ephedrine and pseudoephedrine, two precursors of methamphetamine [100,101]. The d13 C and d15 N values, and later the d2 H values, were reported to enable differentiating natural, semi-synthetic and synthetic ephedrine. Furthermore, as there was no isotopic fractionation during the synthesis of methamphetamine from ephedrine and pseudoephedrine, the analysis of methamphetamine could provide information on the manufacturing process of the precursors used in the synthesis [100,102]. The differentiation of precursors of methamphetamine by IRMS were the subject of two other studies, one on pseudoephedrine samples coming from different manufacturers [103], the other one on batches of P2P [104]. The isotope analysis of methamphetamine highlighted the possibility to differentiate specimens based on their d13 C and d15 N values. However, large d15 N variations (up to 12%) were measured within specimens of methamphetamine, depending on the crystal analysed [105]. Packages of methamphetamine were assumed to contain crystals coming from different ‘‘synthetic batches’’. The authors suggested that the crystal IRMS profiling approach was more appropriate than the measurement of the homogeneised the specimen. David et al. offer a possible explanation for the results obtained by Iwata et al. with their study on isotopic fractionation occuring during the precipitation of methamphetamine [106]. The multiple precipitation steps induced an isotopic fractionation of d15 N and d2 H values, resulting in precipitates becoming gradually more depleted in heavy isotopes. This phenomenon was also related by Casale et al. for the d15 N value of cocaine and heroin [76]. David et al. highlighted that, even specimens produced with the same precursor could present a wide intravariability. The influence of different reaction conditions in the synthesis of methamphetamine on its d13 C, d15 N and d2 H values were evaluated in two studies [107,108]. The isotopic composition of methamphetamine was found to be highly influenced by the d13 C and d2 H values of the precursors. d13 C was not significantly modified by the reaction conditions, emphasising the possibility to link a precursor and its product by means of their d13 C value, while d15 N changed significantly during the synthesis and required further investiga-

Table 4 Ranges of isotopic values reported for MDMA in literature. Study

Method

Number specimens Origin

d13 C %

Mas et al. [87] Carter et al. [88]

16 50

Unknown Unknown

Carter et al. [92]

GC-C-IRMS EA-IRMS GC-C-IRMS EA-IRMS

Palhol et al. [90,91] Carter et al. [86] Billault et al. [93]

EA-IRMS EA-IRMS EA-IRMS

35/106 4 45

Korompay et al. [89] Buchanan et al. [94]

EA-IRMS EA-IRMS

45 18

Buchanan et al. [95]

EA-IRMS

32

4

Controlled synthesis conditions unknown Unknown Controlled synthesis conditions Unknown Controlled synthesis conditions Unknown

d15 N %

d18 O %

29.25 to

27.17

30.65 to 30.42 to

20.98 28.01

28 to 24 28.87 to 28.85 30.4 to 26.0

18.08 to 7.30 4.02 to +20.85

d2 H %

– –

117.00 to

–

–

16 to +19 6.86 to 7.61 8.5 to +17.4

– – –

– – –

–

29.27 to 28.09 28.1 to 26.5

1.94 to +5.11 3.6 to +23.8

– –

30.64 to

1.48 to +28.37

5.01 to 12.18

28.28

– 61.00

93.9 to +6.3

87.15 to

23.8

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

146

tions to understand their origin. In contrast, Salouros et al. did not observe any modification of the d13 C, d15 N and d2 H values of methamphetamine when changing the synthesis conditions of the Nagai and Emde routes [108]. Thus, they could link methamphetamine to the ephedrine and pseudoephedrine used. The inference of the synthetic route based on the d13 C values of methamphetamine was proposed by Toske et al. [109]. The significant differences between the d13 C values of methamphetamine synthesised from ephedrine and pseudoephedrine and from P2P were the basis of a threshold plot to infer the synthetic route of methamphetamine [109]. Nic Daeid et al. reported on the possibility to differentiate methamphetamine synthesised using the Moscow and the Hypophosphorous routes based on its d2 H value [110]. They also observed the influence of precursor solvent extraction and precursor drying over the isotopic signature of methamphetamine. Despite these effects, the differentiation between methamphetamine synthesised from the two routes was still possible. The isotopic information of methamphetamine specimens was combined with the organic impurity profile of methamphetamine [111,105,112]. While the links previously established with investigation and impurity profiling were confirmed in one case [111], the grouping of the specimens with isotope ratios was also reported to be different from the links established with impurity profile [105,112]. Table 5 summarises the range of isotopic values measured for methamphetamine in the different studies. 3.1.2.3. Amphetamine. Amphetamine was also analysed by IRMS [113]. The few analyses showed the possibility to discriminate amphetamine according to their precursor and synthetic route on the basis of d2 H data. The method was presented as an alternative for determining the synthetic pathway of amphetamine specimens, in the absence of route-specific impurities. 3.1.2.4. Legal highs. The potential of stable isotope analysis to link synthesised mephedrone to its precursor was reported in a pilot study undertaken by Nic Daeid et al. [14]. Explaining the chemistry behind the results, they observed reproducible isotopic fractionations between the starting material, the intermediate and the 12 synthesised mephedrone samples. 3.1.2.5. GBL and GHB. The potential of GC-C-IRMS for tracing gamma-butyrolactone (GBL), a chemical precursor of gamma hydroxybutyric acid (GHB), was demonstrated by Marclay et al. through the high repeatability of d13 C measurements on samples of

GBL batches and the wide intervariability observed between 19 GBL lots coming from different chemical providers and internet retailers of different countries [115]. Pazos et al. combined the d13 C value of GBL samples with the websites location distributing GBL, the digital links established between websites and the characteristics of packaging in order to improve the knowledge of the market structure [116]. Chemical information revealed complementary information about the production level and the outflow between retailers and manufacturers. Concerning the detection of GHB in body fluids, the d13 C value of urinary GHB was proposed as an alternative to the concentration cut off limit to differentiate between endogenous or exogenous GHB [117]. In addition, no significant difference was found between the d13 C value of the administered GHB and the urinary GHB, indicating that carbon isotope ratio of GHB could be used for example to establish a link between GHB found in the house of a suspect and the urinary GHB of a person [118]. 3.1.2.6. Synthetic illicit drugs: in essence. From current literature on synthetic illicit drugs, there are two main trends. The first one encompasses studies, in which sampling is based on samples of known sources. They focused mainly on the possibility to differentiate illicit drugs according to the synthetic routes and precursors employed or, for ephedrine, according to their bio or synthetic origin. Conversely, the second category of studies involved specimens seized by law enforcement, and therefore of unknown ‘‘source’’. Studies in this category mostly concern caseworks or case-to-case comparisons. As specimens are of unknown source, the definition of the notion of source in these studies has not been addressed and a generic expression such as ‘‘specimens came from the same source’’ has been used. At present the definition of the source in the isotopic analysis of illegal synthetic drugs has been mainly focused on the synthetic route and the precursors used. However, Buchanan et al. showed the isotopic profile was of limited use to infer the synthetic route, as it varies within a synthetic route despite controlled conditions [94]. In addition, modifications of the reaction conditions within a synthetic route induced significant isotopic differences between batches of MDMA produced with the same batch of precursors and reagents [95]. This was considered as a complex issue by Buchanan et al.. In light of these results, studies involving specimens of unknown sources and concluding on the common source of some synthetic drug exhibits may well be unsettled, and in search of a new meaning of ‘‘source’’. However, the high variability and poor reproducibility of the isotopic profile within a synthetic route may

Table 5 Summary of data on the isotopic analysis of methamphetamine reported in literature.

d13 C (%)

d15 N (%)

Study

Method

Number specimens

Origin

Carter et al. [92] Kurashima et al. [100]

GC-C-IRMS EA-IRMS TC/EA-IRMS

Iwata et al. [111] Collins et al. [102]

EA-IRMS TC/EA-IRMS

Iwata et al. [105] David et al. [106]

EA-IRMS EA-IRMS

David et al. [107]

EA-IRMS TC/EA-IRMS TC/EA-IRMS EA-IRMS EA-IRMS GC-C-IRMS EA-IRMS

Synthesised Synthesised Unknown Synthesised Unknown Unknown Synthesised Unknown Unknown Synthesised unknown Synthesised

29.34 to 29.01 33.1 to 25.5

Kurashima et al. [101]

4 4 21 7 25 39 23 32 3 8 38 53 27 7 29 48

Salouros et al. [108] Tsukijawa et al. [112] Toske et al. [109] Nic Daeid et al. [110]

32.8 to

23.1

d2 H (%)

+0.56 to +7.73 11.1 to +10.9 3.2 to +9.4

237 to +47

29.40 to 24.90 27.7 to 21.0

2.29 to +5.94 1.5 to +11.4

193 to +145

25.14 to 24.65 28.0 to 27.7 29.3 to 23.7 29.5 to 23.1

7.61 to +6.08 8.0 to +17.2 10.1 to +6.1 +0.2 to +17.7

17 to +8 264 to +63 138 to +168

Synthesised Unknown Synthesised

30.0 to 33.8 to 37.2 to

0.7 to +12.3 +4.0 to +5.6

Synthesised

27.35 to

22.6 30.6 24.0 24.21

3.24 to +8.20

174 to +151

154.4 to +66.2

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

be perceived differently. Indeed, the wide variability of the multielement isotopic profile may not be traceable to a specific synthetic route, but may offer the possibility to differentiate production batches of MDMA, meaning that the ‘‘poor’’ reproducibility of synthetic conditions may constitute a certain degree of ‘‘specificity’’ of the batch. This hypothetical ‘‘specificity’’ is supported by the fact that illicit synthetic drugs may be manufactured in a less controlled manner than scientific bench experiments. These uncontrolled conditions would induce an even wider variability and lead to production batches with highly variable isotopic profiles. This hypothesis needs obviously to be studied and evaluated through intra and intervariability of production batches. On that point, measured d values were reported with small standard deviation for triplicate analysis, providing a preliminary indication on the isotopic homogeneity of the batches. Yet, these experiments were conducted on a small-scale and, in any case, do not replace a thorough evaluation of batch intravariability. The evaluation of the isotopic variability at such level of source would not indicate that specimens with similar isotopic profile had been synthesised following the same synthetic route, but rather that they came from the same production batch. This hypothesis necessitates of course to be evaluated and require fundamental data on variability. Intervariability is commonly well measured as it easily shows the discrimination power of the technique. In contrast, intravariability data are unfortunately missing for both samples of known and unknown sources, suggesting that variability within a specimen or within a production batch could be overlooked. This lack of knowledge may lead to underestimation of inherent variability and overdetermination of the signification of apparent different isotopic values, prejudicing interpretation of isotopic data. Compound specific isotope analysis (CSIA) appears more adequate to deal with the complex matrix of illicit drugs, as they often contain numerous compounds (impurities, active substance, cutting agents). Except for pure illicit drugs, bulk analysis offers a less transparent result. Finally, a most peculiar and worrying issue is the far-fetched apparition of DR (dynamic range) notion to evaluate the evidentiary value of the isotopic profile of an ecstasy specimen stored in a database [4]. The ‘‘Dynamic Range’’ (DR, unitless) of the d value is defined ‘‘as the isotopic range for a given suite of samples divided by the typical standard deviation of a replicate measurement of the same’’ [4]. By multiplying the DR for each isotope, the final figure provides the probability for a random match. This approach is questionable, as it does not take into account the distribution of the population and does not consider the specimen homogeneity. 3.2. Human provenancing Human provenancing is based on the analysis and interpretation of stable isotope ratios in human tissues to determine the geographical origin and life history of a person [3,4]. Although the isotopic analysis of human tissues in forensic caseworks is rather recent, Katzenberg and Krouse already evoked the possibility of using stable isotope variations in human tissues for forensic investigations in 1989 [119]. They highlighted the potential of combining the isotopic composition of different tissues and fluids to provide information on the geographical long-term residence and the recent travel of an individual. The use of isotopic information in a forensic intelligence perspective was already mentioned. The first published case involving the exploitation of stable isotope analysis on human remains, the ‘‘Adam’’ case in London, only dates back to 2001 [20]. Five other caseworks reported on

147

human provenancing in forensic investigations [4,121–123]. The limited applications to caseworks, and the few rare forensic background studies on this topic may raise skepticism on the possibilities of such an application. However, a detailed scrutiny of literature reveals that the knowledge constituting the basis of this science derives from earth science works and from numerous applications in the study of ancient cultures remains. The relationship between the isotopic profile of human tissues and the diet or the environmental conditions of an individual has been much investigated and exploited in archaeology to extract information on paleodietary or paleoenvironmental conditions [124–127]. As mentioned earlier, the relationship between the isotopic signature of animal tissues and its diet also prevail for any other organism involved in the food chain. As such, the isotopic analysis of human tissues and fluids may reveal its diet, and hence its dietary habits and geographical environment [122]. Reference data from worldwide regions can be used to differentiate geographical regions. In order to interpret isotopic values of human tissues, global databases, isotope maps, also known as isoscapes illustrating the spatial distribution of isotopic variations [128,129], as well as prediction maps and models for isotope spatial pattern [130,131] have been developed. One major element of exploitation of this information is based on the time at which the tissues of a human body are formed, as well as on their turnover rates [119,121,132]. As the isotopic composition of the tissue reflect diet and environment at the time of formation of the tissue, the combination of the isotopic signatures of several tissues reveals information on the geographical residence and trajectories of a person on long and short-term scale. Probably because of the non-invasive character of its sampling, hair is the most studied medium from which isotopic information is extracted [119,123,126,133–141,130,142–146]. Other media studied for their isotopic composition are fingernails [134,138,140,142], teeth enamel [125,147–150,145] and bone collagen [124,134,125]. Stable isotope ratios may help in the identification of a person (disaster victim identification, counter terrorism investigations or illicit immigration identification), when other evidence such as fingerprints or DNA are not exploitable or available. The following applications demonstrate the potential of isotopic information to reconstruct the life history and geographical movements of an individual. The information conveyed by stable isotopes provides intelligence to assist investigations. Such intelligence is complementary to the information given by other investigating strategies and may allow for example focusing the search of the identity of a person in databases of a specific geographic area or in a given environment. In 2001, the torso of a child was discovered in the River Thames [4]. In the absence of identifying features on the dismembered body, the isotopic analysis of bone enabled the exclusion of several geographical regions. In order to evaluate the time spent by the victim in the United Kingdom, working on skin and fat samples of the victim, a significant change in diet 4 weeks prior to the death of the child was observed. However, the true identity of the child and his family has not been discovered yet. In 2002, the decomposed human body of an unidentified person was discovered buried near an expressway in Germany [121]. Isotope ratios from hair, skull and teeth, completed by a dental work expertise, suggested the person was born and had lived in Romania. Using this information, the police was able to formally identify the body through the DNA analysis of members of a family and arrested two men responsible for the death of the victim. In the ‘‘Scissor sisters’’ case, stable isotope results provided intelligence for the investigations on the life history and geographic origin of a dismembered and decapitated murder victim discovered in 2005 [122]. This led to several possible identities for the victim. Family cross-DNA analyses allowed the

148

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

identification of the victim and the presumed geographic origin and life history were confirmed by the police. Two sisters, that became the major suspects of the case, confessed having committed the crime. Meier-Augenstein reported two other cases of human provenancing [4]. The first case concerned an Asian young man that succumbed to multiple stab wounds in a hospital in the UK. The identity of the victim was established on the basis of a hit in the Interpol fingerprint database. However, his entry in the country was not referenced anywhere. Stable isotope analysis of hair provided information on where the person had lived prior to death, and how long he had been living in the UK. Parallel police investigations confirmed the life history. The second case involved the multi stable isotope analysis on scalp hair and tooth enamel of unidentified remains of an adult male discovered in 2001 in Newfounland island, in Canada [4]. The isotope information enabled the exclusion of several regions. The identity of the victim had not been established yet at the time of the publication. Kennedy et al. reported the isotopic analysis of human scalp hair of an unidentified woman found in Utah in 2000 [123]. Specific d18 O values could be related to two geographical regions. It is however not mentioned if the information was communicated or exploited by law enforcement. The case of a dead new-born found in Germany is reported by Lehn and Graw [132]. Isotopic analyses were used to obtain information on the origin and place where the mother stayed during pregnancy and she was finally identified. 3.2.1. Human provenancing: in essence Rauch et al. and Lehn and Graw raised important issues regarding the interpretation of isotopic data [121,132]. They recalled the need of fundamental research on the turnover-rates of human tissues as well as physiological parameters, and the need for more reference data. Meier-Augenstein highlighted the potential as well as the limitations of such analysis in human provenancing [4]. Indeed, even isotopic data in combination with information on diet, may not be sufficient to determine the precise region of origin of an individual. It is however interesting to examine the context and use of this information. The measurement of stable isotope ratios to infer the geographical provenance of individuals in a forensic perspective has been mainly undertaken in high profile cases, when other techniques could not establish the identity or provenance of the person. In the cases reported above, the isotopic information was used to generate intelligence and to orientate investigations, rather than for its evidentiary value in court. It can also be used to confirm or exclude hypothesis of geographical regions made by the police. In any case, the isotopic information should be interpreted in the context of the case and in conjunction with other elements, and not as the only piece of the puzzle. The presented cases attest to its potential as intelligence. Compared to other forensic applications, its main use as intelligence in the case of human provenancing is probably due to a larger awareness of the level of uncertainty associated with the trace. The ignorance of such uncertainty can lead to miscarriages of justice or worrying and controversial projects, such as the one proposed by the British government in 2009 [151]. The project, which suggested the use of isotopes to determine the true country of origin of asylum seekers, was eventually abandoned in 2011. 3.3. Ignitable liquids Most publications on the isotopic analysis of petroleum products concern environmental forensic science. Research about the isotopic analysis of ignitable liquids within the frame of fire investigation is relatively limited. While IRMS is applied in both fields in a source inference perspective, the research problem, sampling, method and factors influencing the isotope ratios are

different. Only studies relevant to fire investigation are reported in this section. Among the rare publications in this field, gasoline was the most studied ignitable liquid [34,152–155]. IRMS was also applied to MTBE [34,153], an additive in gasoline, diesel fuels [156–158] and household ignitable liquids [159]. While the compound specific measurement of d13 C and d2 H values was the common approach, the potential of bulk analysis was also compared to that of CSIA in some studies [153,155]. Smallwood et al. could differentiate 19 gasoline samples collected at gas stations in different areas in the USA, based on the d13 C values of 16 selected compounds [152]. O’Sullivan and Kalin also reported the discrimination of 28 gasoline samples from different country, despite the close d13 C values of the 19 selected compounds [153]. Heo et al. collected 40 gasoline samples from four companies in South Korea [155]. The gasoline produced by two of the four companies showed different bulk and compound specific carbon and hydrogen values. When extracting gasoline compounds by headspace singledrop microextraction (HS-SDME) prior to their isotopic analysis by GC-C-IRMS, Li et al. observed no d13 C isotope fractionation [154]. The effect of evaporation [152] and water washing on the isotopic profile of gasoline was investigated. The results of Smallwood et al. suggested that all compounds in gasoline were not equally affected by weathering factors [152]. A preliminary study on MTBE was undertaken by Smallwood et al. [34]. The d13 C and d2 H values of 3 samples of MTBE purchased from different distributors, as well as of the MTBE contained in 10 gasoline samples collected at service stations from 3 different areas in the USA, showed that GC-C-IRMS could be used to differentiate sources of MTBE. Additional data on MTBE were published in [153]. From these studies, it appears that MTBE samples or MTBE found in gasoline can be differentiated based on their isotopic signature. Harvey et al. reported the differentiation of 4 diesel fuels coming from different locations, based on the compound specific d13 C and d2 H values [156]. The same isotope ratios of selected compounds were analysed by Muhammad et al. in order to distinguish 45 samples of diesel coming from 9 service stations in the South Island of New Zealand [157]. Further experiments on the progressive evaporation of one diesel sample over 21 days was undertaken and showed that the specific d13 C value of n-alkane compounds and the d2 H value of the less volatile n-alkanes (< C18) were not significantly altered [158]. The carbon isotopic fractionation induced by realistic combustion conditions was investigated by Schwartz et al. with four types of household ignitable liquids [159]. The compound specific analysis of the residues extracted from burnt carpet revealed changes in the d13 C values from 0 to +10%: The non predictable isotope fractionation induced by combustion appears at present as a limitation in the application of IRMS to fire debris. 3.3.1. Ignitable liquids: in essence The applications of IRMS to flammable liquids focused on its capacity to discriminate different sources of the product. It is interesting to note the variety of sampling of the studies. Samples came from different distributors [34], gas station [152], countries [153], companies [155], locations [156]. As the question of the source and the sampling are highly interconnected, the notion of source in these studies should be defined. Indeed, the level of source that can be inferred is often unclear. 3.4. Explosives Much preliminary research has been undertaken on a wide range of explosives and is described below. The following studies are then categorised between preblast and postblast, and organic and inorganic studies. The categorisation is respected as far as

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

149

Table 6 Summary of reported results on the bulk isotopic analysis of TNT in literature. Number specimens

Study Nissenbaum [165] *

Finnigan [73] Coffin et al. [166] Widory et al. [167] Lock [168]

7

d13 C (%)

Origin UK, USA, Israel, Italy, Canada, Yugoslavia, Hungary Germany, Russia, Unknown USA, Croatia Montenegro, France Unknown

3 5 14 5

30.93 to

30 to 26 26.42 to 22.21 29.9 to 23.5 28.80 to 27.14

possible, as many studies often reported on several types of explosives at the same time. Pilot studies: Many preliminary or pilot studies were conducted on a small scale with few samples. Although the results were rather limited and not published in peer-reviewed journals, these studies were among the first exploratory applications of IRMS to explosives. They drew the attention of forensic scientists to the potential of IRMS to differentiate explosives coming from different sources. IRMS was applied to TNT [73,160,161], ammonium nitrate [160–162], black powders [160,161], plastic explosives [160,161], PETN [162,163], RDX [162,164], HMX [162], nitroglycerin [164] and various other explosives and substances found in improvised explosive charges (sodium chlorate, nitromethane, sugar, nitrocellulose, flashpowders and perchlorates) [160]. 3.4.1. Preblast studies 3.4.1.1. TNT. In 1975, Nissenbaum published results on the isotopic analysis of 7 samples of 2,4,6-trinitrotoluene (TNT) coming from different countries [165]. The wide range of d values showed the potential of IRMS to differentiate specimens of TNT based on their carbon isotopic variations. Coffin et al., Widory et al. and Lock also published results on the isotopic analysis of TNT [166–168]. It is interesting to see that the ranges of reported d13 C and d15 N values are wide. Except for Coffin et al., who analysed TNT samples using GC-ion trap-mass spectrometer (ITMS)-IRMS, the other authors used EA-IRMS. Table 6 summarises the range of isotopic values of TNT reported in the different studies. 3.4.1.2. Semtex. The d13 C and d15 N variations of seized Semtex, assumed to come from different sources, were evaluated using a likelihood ratio (LR) framework [169]. The authors showed that the misleading evidence rate varied depending on the chosen probability distribution and highlighted the necessity to have large stable isotope ratio databases to use this approach. Lock obtained similar d13 C and d15 N values on a set of 16 Semtex specimens [168]. Table 7 displays the ranges of bulk isotopic values of Semtex reported in the two studies. 3.4.1.3. PETN. Benson et al. undertook a preliminary study on the potential of IRMS to distinguish 15 Pentaerythritol tetranitrate (PETN) specimens coming from the filling of different detonating cords and boosters [170]. All the specimens could be differentiated based on their bulk isotope signature. The d13 C and d15 N values covered a larger range than those measured in [167]. Widory et al. analysed the bulk isotopic profile of 12 PETN samples [167], as well as that of ammonium nitrate fuel oil and TNT. The combination of Table 7 Summary of reported results on the bulk isotopic values of Semtex in literature. Study

Number specimens

Origin

Pierrini et al. [169] Lock [168]

26 16

Unknown Unknown

24.53

*

d15 N (%)

d18 O (%)

d2 H (%)

–

–

–

– – +16.5 to +19.2 –

– –

0.5 to 1.5 5.36 to +9.64 8.7 to +3.5 5.93 to 1.68

103 to

60

–

the elemental concentration and isotopic signatures was used to differentiate the types of explosives (PETN, TNT and ammonium nitrate based explosives). Although the combination of information is a valuable approach, the relevance and forensic aspect of the study is largely questionable, given the cost and complexity of IRMS. Other methods routinely employed enable the identification of the explosive. Howa et al. measured the isotopic variations of 175 samples of PETN coming from 22 manufacturing facilities and presented the isotopic relationship between reactants and products in PETN synthesis [171]. They assessed the withinsample and within-block variability and reported on the discrimination of explosive blocks of PETN coming from the same manufacturer. The d13 C value of PETN showed to be similar to that of the reactant, while its d15 N value was more negative than nitric acid. Table 8 3.4.1.4. Hexamine. The isotopic variability between 14 samples of hexamine coming from chemical suppliers was evaluated with statistical methods (HCA, ANOVA and Tukey comparison) [4,172,168]. Additional data on 17 samples hexamine coming mostly from different chemical suppliers were later published [173]. The ranges of values measured for hexamine are summarised in Table 9. 3.4.1.5. Research department explosive (RDX). Lock and MeierAugenstein published data on the signature of RDX and the isotopic fractionation during its synthesis from hexamine [4,172]. The d13 C and d15 N variability measured within 2 batches was reported to be small. Following one synthetic route, with the same reaction conditions and reagents, they observed a systematic and reproducible isotopic fractionation for carbon and nitrogen. They concluded that it might be possible to predict the signature of the starting material from RDX specimens, based on the linear relationship between the reactant and product. Additional data on RDX were reported in [168] with the extraction of RDX constituent from C4 explosives by pentane. The d13 C and d15 N values of both RDX and the C4 explosive were measured and compared. Howa et al. collected RDX samples from 12 factories, as well as reactants and side-products (HMX) associated with the sampled batches from 3 manufacturers [174]. The carbon isotopic relationship existing between RDX and its reactants was found to be similar as the shift reported by Lock [172]. For nitrogen, different isotopic fractionations were measured for the two processes used to manufacture RDX. Although the ranges of isotopic values are larger than any values reported in literature, note however that RDX and HMX were purified before their isotopic analysis.

indicates d values estimated from plots.

d13 C (%) 36.53 to 38.00 to

d15 N (%) 24.76 26.06

25.68 to 22.43 to

d18 O (%) 2.72 4.57

– +17.10 to +33.05

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

150

Table 8 Summary of reported bulk isotopic values of PETN in literature. Study

Number specimens

Origin

Benson et al. [170]*

8 7 12 175

Unknown

Widory et al. [167] Howa et al. [171]

*

indicates d values estimated from plots.

d13 C (%)

d15 N (%)

25 to 3 48 to 28 38.4 to 29.0 49.7 to 28.0

Montenegro, France Manufacturing facilities

12 to +4 15 to 1 16.3 to 5.1 48.6 to +6.2

d18 O (%)

d2 H (%)

–

–

+16.1 to +22.9 –

–

64 to +20

Table 9 Summary of reported results on the bulk isotopic analysis of hexamine in literature.

d13 C (%)

Study

Number specimens

Origin

Lock [168] Lock [173]

14 17

Chemical suppliers Chemical suppliers

46.18 to 52.13 to

Table 10 3.4.1.6. TATP and precursors. Benson et al. searched for correlation between the reaction conditions and the d13 C value of triacetone triperoxide (TATP) samples [170]. In addition, they reported the differentiation of 18 TATP samples synthesised under different conditions based on their isotopic signature. Acetones from different distributors and from laboratory inventories were discriminated based on their d13 C and d2 H values. The approach was completed with the analysis of trace constituent by GCxGC, when the isotopic signature of the samples was similar [175]. In 2007, in the case of R.v. Ibrahim and others concerning the attempted London bombings on the 21st July 2005, one of the defendants stated that the hydrogen peroxide, used in the hydrogen peroxide–flour mixture, had an initial concentration of 70%, but had been diluted with tap water to reach a concentration of 35%. According to the judgement, based on the comparison of the isotopic composition of London tap water and the isotopic signature of the explosive charge, the expert claimed that the defendants contention was ‘‘impossible’’ [176,177]. Lock studied the isotopic variations of hydrogen peroxide (H2O2) samples coming from 7 different suppliers [168]. Two samples coming from the same batch, but from different bottles could be grouped using HCA statistical analysis. Probably in connection with the argument alleged by one of the defendants [176] in the context of the London bombings, the possibilities to link a diluted H2O2 solution with the original one and to provide information on the water used to dilute it was also investigated. Concentrated H2O2 was diluted with deionised water and mathematical regression was applied to predict the isotopic values of the original substance and water. Another group of

d15 N (%) 34.51 34.75

2.48 to +0.41 2.45 to +1.06

d2 H (%) 83.89 to +55.16 –

authors extended the knowledge on the isotopic ranges of H2O2, by analysing 97 H2O2 from USA and Mexico [178]. The isotopic signature oscillated on a large scale, indicating that they could be used to differentiate samples. Supplementary data on H2O2 were published by Lock et al. in a paper, where they also reported the isotopic relationship existing between the explosive hexamethylene triperoxide diamine (HMTD) synthesised from hexamine and H2O2 [173]. Under controlled laboratory conditions, they observed a linear relationship between the d13 C values of the precursors and products. In field experiments, the varying conditions induced larger d15 N variations, rendering more difficult results interpretation. The ranges of values of hydrogen peroxide measured in literature are summarised in Table 11. 3.4.1.7. Weed killer. Weed killers, employed as oxidant in homemade explosive compositions, were also the object of an isotopic study [179]. Ader et al. observed limited d37 Cl variability between 4 chlorate and 3 perchlorate based compounds. Interestingly, and similarly to what was reported in [106,105], the isotopic differences noticed between crystals of sodium chlorate are likely to originate from the isotopic effect associated with the crystallisation step. 3.4.1.8. Black powder. After the exploratory study of Wakelin [160], Lock analysed 18 specimens of black powders coming from caseworks [168]. Although groups of specimens were highlighted with HCA and PCA analyses, their interpretation was difficult, as the source of the specimens was unknown. Gentile collected samples of black powder from 3 manufacturers, representing 5 different types and 33 batches [180,57]. The exposition of black powder to different environmental conditions showed to have a

Table 10 Ranges of isotopic values of RDX reported in literature. Study

Number specimens

Origin

Lock et al. [172] Lock [168] Howa [174]

5 12 100

Unknown Unknown Factories

d13 C (%) 38.34 to 26.23 45.37 to 22.18 49.5 to 16.6

d15 N (%) 15.62 to 13.79 8.91 to +4.59 17.4 to +8.5

d18 O (%) 37.07 to

36.52

– –

Table 11 Ranges of bulk isotopic values of hydrogen peroxide reported in literature. Study

Number specimens

Origin

Lock [168] Barnette et al. [178] Lock et al.[173]

10 97 34

Chemical suppliers USA, Mexico Chemical suppliers

d18 O (%) 1.90 to +13.43 8.8 to +15.3 6.57 to +13.43

d2 H (%) 132.9 to 18.8 235 to 5 147.07 to 18.78

N. Gentile et al. / Forensic Science International 251 (2015) 139–158 Table 12 Ranges of isotopic values of black powders reported in literature.

*

151

indicates d values estimated from plots.

d13 C (%)

Study

Number specimens

Origin

Wakelin [160]* Lock [168] Gentile [180,57]

8 18 33

Unknown Unknown Manufacturers types batches

significant influence on its d15 N value. Unsupervised and supervised statistical methods were used to differentiate samples according to three distinct levels of source: the manufacturer, the type and the batch of black powder. The possibility to use the models in a forensic context was discussed. Table 12 displays the ranges of isotopic values of black powder reported in literature. 3.4.1.9. Ammonium nitrate. Benson et al. provided fundamental data on the d15 N variability of ammonium nitrate prills within the production of 3 Australian manufacturers over one year [181,182]. She evaluated the discrimination power of IRMS on the Australian samples, as well as 20 overseas samples. The large d15 N variations measured within manufacturers’ production over 12 months ranged from 1% and 4.3%. In the absence of changes in the manufacturing process, this variability raises questions on its origin, in addition to issues on sampling and its representativeness for mass produced substances. As corroborated by the limited range of d15 N variations reported in literature, the d15 N values only offered limited discrimination between Australian manufacturers. Australian manufacturers and overseas sources could be differentiated based on d18 O and d2 H data, although discriminiation was limited due to overlap. The isotopic data could nevertheless provide investigative support. The authors published the validation of the method for the analysis of bulk d15 N value in ammonium nitrate [183]. Lock analysed 41 samples of ammonium nitrate prills, some from known manufacturers or countries, others from unknown origin [168]. PCA and cluster analysis revealed the existence of several groups between the samples. However, interpretation of data was difficult, as some groups overlapped and the origin of some samples was unknown. The isolated ammonium and nitrate ions of 42 ammonium nitrate prill samples were analysed for their d15 N values [184]. This approach was viewed as more discriminatory than bulk analysis. However, there was no comparison to the bulk d15 N values of the samples and the treatment of the differentiation of the samples was not convincing. Gentile analysed samples of ammonium nitrate prills coming from 13 different batches from different manufacturers [57]. The storage of the samples under different environmental conditions over one year had no significant influence on the d15 N and d18 O values. Unsupervised and supervised statistical methods were evaluated to differentiate the samples and the applicability of such models were discussed in a forensic context. Table 13 summarises the range of bulk isotopic values presented in the different papers. 3.4.1.10. Urea nitrate. Aranda et al. showed interest in the isotopic relationship existing between precursors and the synthesised urea Table 13 Ranges of isotopic values of ammonium nitrate reported in literature.

*

28.5 to 26.0 27.47 to 25.59 28.6 to 26.4

d15 N (%) 27.0 to +5.0 16.93 to +8.33 28.0 to +2.9

d18 O (%) +12.0 to +24.0 +14.29 to +28.87 +15.0 to +24.2

nitrate [185]. The d13 C value of bulk urea nitrate was indistinguishable from that of the urea precursor, while the d15 N values of isolated urea and nitrate ions reflected that of the urea and nitrate used for the synthesis. Factors, such as the size of the batch and temperature variations, did not influence the isotopic signature of the product. They also highlighted the possibilities to differentiate urea nitrate specimens. 3.4.2. Postblast studies While several short communications indicate that there has been exploratory research on the isotopic analysis of explosives residues, very little data have been published on the subject [99,186]. McGuire et al. were the very first to report the isotopic analysis of postblast residues of HMX, TNT, octol, TATB (1,3,5-triamino2,4,6-trinitrobenzene) and 3 plastic bonded explosives [187]. Except for the d13 C values of aromatic explosives which appeared almost unchanged, that of other explosives underwent isotopic fractionations upon detonation. d2 H and d15 N values were also affected by explosion. Using isotopically labelled molecules of TNT of comp B explosive, Anisichkin et al. observed that the tag atoms were shared out among the different gaseous and condensed carbon products after detonation [188]. Benson et al. investigated the postblast d15 N value of ammonium nitrate based explosives, by detonating 6 explosive devices in duplicates, with varying improvised and commercial charges and boosters [181]. A significant isotopic d15 N enrichment of residues was observed and potential explanations were provided. Residues of explosives are collected on a variety of surfaces and, or extracted from samples of soil. Numerous environmental studies discuss the effect of external factors on the recovery and stability of the isotopic signature of explosives. Isotopic fractionation may occur due to moisture and bacterial degradation in soil [166], microbial processes in water [189,190], soil and on some surfaces [190]. 3.4.3. Explosives: in essence Explosives is a flourishing field of applications of IRMS. The number of short communications demonstrate the numerous groups of researchers exploring the subject. However, given the abbreviate format of the pilot studies, it is difficult to grasp the amount of work that has been done so far. Among the published studies, a number of paper focused on several explosives at the same time. Although this approach provides indications on the possibility of IRMS to discriminate specimens of explosives, it often produces exploratory data and lacks for fundamental aspects. The absence of hypothesis on the source level, and especially the absence of within variability (intravariability) measurement,

indicates d values estimated from plots.

Study

Number specimens

Origin

Widory [167] Benson [181,182]*

4 79

Lock [168] Gentile [57]

41 13

France commercial handcrafted Australian overseas Manufacturers unknown Manufacturers types batches

d15 N values (%)

d18 O values (%)

d2 H values (%)

2.4 to +0.8 2.3 to +2.0 4 to +1.4 1.83 to +2.22 6.1 to +2.1

+21.6 to +23.3 +13.0 to +20.5 +12.5 to +21.5 +13.18 to +26.20 +16.5 to +24.4

237 to 170 30 to +80 25 to +45 – –

152

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

prejudices interpretation of the results [191]. All the studies report the capacity of IRMS to discriminate the analysed samples. However, the evaluation of intervariability is not possible without data on intravariability. Measuring a large range of isotopic values between the productions of manufacturers appears useless for their discrimination, without a knowledge on the within variability. Very few studies allocated sufficient attention to the evaluation of this parameter. Often, intravariability is mistakenly presented through the standard deviation of replicates of the specimen. This however does not reflect the isotopic variations in the material (although it may provide an indication), but the precision in measurement. The same applies to the uncertainty of the method, which is also sometimes presented as such. Conversely, this simplification of the problem can only result in a misleading underestimation of intravariability. Furthermore, the rare available data showed that the variability within a source could be large. As for other massproduced substances, an evaluation of the homogeneity of the isotopic profile often show larger variations than expected. For these reasons, intravariability should not be overlooked, but measured at the same time than intervariability The notions of intra and intervariability are directly related to the definition of the source. As for illicit drugs, the fact that the definition of the source is often absent or ignored in paper on explosives likely ensues from the analysis of specimens coming from caseworks or seizures. Although establishing the level of source in such cases is not simple, it should be highlighted that a statement such as: ‘‘...they come from the same source’’ does not mean anything without more details on what is meant by source. While the definition of the source is left to the appreciation of the reader in many papers when IRMS is used for discrimination purposes, one clearer dimension that IRMS may elicit is the source as the starting materials or product of a synthesis [172,174,185,171]. The prediction of the signature of the starting material or product may be possible when the isotopic values are inherited from the precursors with limited variations. However in some cases, the reaction yield and conditions may have a non negligible influence on the isotopic signature of the product [173], as also noticed in the synthesis of illicit drugs [95]. Most studies on the isotopic analysis of organic explosives reported data obtained with bulk analysis. However, a new tendency towards the extraction of the explosive component from the matrix is emerging. CSIA would offer a finer analysis of the explosive composition, separating the explosive substance from its additives, such as binders, stabilisers, etc. However, the discrimination power of such an approach remains to be demonstrated. Finally, there has been limited research in the analysis of postblast residues and their comparison with the initial explosive so far. Actual results show that explosion induces an isotopic fractionation. In addition, external factors may influence the isotopic signature of explosives remaining in soil or water. At present, the exploitation of isotopic data in a postblast context remains a challenge. 3.5. Other applications 3.5.1. Paints After the exploratory analyses undertaken by Finnigan MAT on paints and varnish [73], two studies focused on architectural white paints. The first study reported on the d13 C values of 28 paints of unknown origin [192]. The homogeneity within a layer of paint was evaluated, as well as the weathering of a 3-layers paint under controlled conditions. Solvent evaporation was presented as a likely explanation of the depletion of 13 C measured after weathering. The authors highlighted the need for further studies on heterogeneity and long-term weathering. In the second study, the similarity of the isotopic profile of 51 white paints coming from eight brands was evaluated using likelihood ratios [193]. Despite

small false positive and false negative rates, it appears unclear what the LR values indicated without an explicit definition of the notion of source. 3.5.2. Soils Croft and Pye studied the spatial and temporal d13 C and d15 N variations of soils [194]. Sampling soil in the same place over two years, they did not notice any significant carbon and nitrogen isotopic variations. Experiments involving the primary transfer of soil on shoe soles showed not to affect the isotopic signature of soil. Isotopic data was used in combination with colour, particle size and elemental composition to discriminate between soils coming from 5 geographical locations [195]. The d13 C and d15 N values enabled a good discrimination of the samples. However, the complexity to interpret nitrogen isotopic variations in soils was highlighted, as the nitrogen composition may depend upon factors, such as fertilisers, according to the period of time in the year. Further research on the spatial variability of soil characteristics was undertaken on two sites [196]. Although each site could be distinguished, the results especially underlined the important intravariability. 3.5.3. Fibers In order to fight against false declaration on the country of origin of cotton, the analysis of cotton by IRMS was used to infer the geographical origin of the samples. A first succinct study presented the discrimination of undyed cotton samples coming from Egypt, Argentina, Turkey and Uzbekistan on the basis of the d13 C, d2 H and d18 O values [197]. The second study reported the successful use of the isotopic signature to discriminate between unprocessed US and non-US cotton samples [198]. These results are encouraging, however, the use of this technique is not applicable in caseworks where very small amounts of material are available. An evolved EA-IRMS system was proposed to deal with such issues [199]. 3.5.4. Tapes Various types of tapes (masking tape, packaging tape, adhesive tape, PVC tape) were analysed by IRMS using d13 C alone [86,200,201] or associated with d2 H [85,202] and d18 O [203]. The potential of discrimination was assessed with samples coming from batches and sub-batches [85], from local suppliers and parcels delivered to the laboratory [203], from different brands [202,201] and manufacturers [200]. In most research, the methodology involved the separate analysis of the backing material [85,203,202,201] and of the adhesive fraction [85,202]. The differentiation of tapes was reported to be better with the analysis of the backing material [85] or even with the analysis of the untreated tape (backing and glue) [203]. Existing data on intravaribility reported small isotopic variations measured within a roll [201] and within a manufacturer [200]. The d13 C value [201], or its association with d2 H [85,202], enabled a good discrimination of the tapes. Aziz et al. showed that isotopic analysis of the tapes corroborated their differentiation based on their GC-MS profile. In order to evaluate the influence of the concealing of packaged drugs in water tanks on the isotopic signature, experiments involving the storage of packaging tapes in water were undertaken [203]. The original isotopic composition of the tapes was not altered by the storage conditions. Similarly, Dietz et al. showed that the effect of explosion had no significant influence on the d13 C value of the tapes they analysed, making d13 C measurement of tapes a interesting tool in explosives investigations. The d13 C values of masking tapes were used in caseworks in order to evaluate whether two cases involving the smuggling of money were linked [86]. The masking tape of the two cases were found to be isotopically distinct, leading the authors

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

to suggest that the tapes were not linked. Likelihood ratios were used to evaluate whether two samples of duct tapes came from the same batch [204]. This was assessed based on the physical and isotopic characteristics of 20 duct tapes. 3.5.5. Plastic Most samples of cling film analysed in [78] coming from heroin seizures and of retail could be differentiated, based on d13 C, d2 H and d18 O values. The combination of bulk d13 C and d2 H data to physical characteristics of grip-seal plastic bags commonly found in drug seizures was reported by Taylor et al. [205]. Bags with different isotopic composition were concluded to likely come from different manufacturers or production batches, although the description of their sampling did not appear to be consistent with such statement. IRMS was applied to the plastic composing two-ways radios by Quirk et al. [206]. The d13 C and d2 H values between the plastic of the detonated and intact radios were in close agreement, indicating the possibility to associate fragments of radio on an explosion scene with the one used to transmit the detonation signal. 3.5.6. Safety matches In order to evaluate the isotopic profiles of matches in a criminal case, Farmer et al. analysed matches from 9 brands manufactured in EU (European Union), Czech Republic, India and USA [207,208]. The d13 C, d18 O and d2 H values enabled the differentiation of matches made of wood coming from trees grown at different geographical locations. The eventual isotopic comparison of the evidentiary matches and the seized material suggested different sources. They also compared unburnt and burnt wooden matchsticks and tested whether the addition of petrol and the use of fire extinguishers could alter the isotopic profile [209]. Overall, the d13 C, d18 O and d2 H values of unburnt and burnt matches, with added petrol or extinguished by different means, were statistically indistinguishable. 3.5.7. Microbial studies The microbial application of IRMS in forensic science was largely initiated by the anthrax terrorist attacks in the USA in 2001, referred to as the Amerithrax case [210]. These bio-weapons attacks involved the mailing of envelopes containing spores of anthrax to news media offices and 2 US senators [211]. Stable isotope ratio analysis was used to provide information on the potential geographic location from which originated the culture of the anthrax spores and on the growth medium. Horita et al. reported that the isotopic composition of 2 strains of microbial agents grown under controlled conditions was predictable, as it reflects the media and substrates isotopic signature [212]. Similarly, Kreuzer-Martin et al. reported the bulk isotopic analysis of microorganisms to infer the source of bioterrorism acts [213–217]. Evaluating the within-batch and between-batches isotopic variations, they reported that the isotopic profile could be used to differentiate batches of microorganisms grown under the same conditions. The d2 H and d18 O values of growing cells and spores were shown to be directly related to those of the media water, confirming that these parameters could be useful to trace the geographical origin of microbial cultures [213,217], while their d13 C and d15 N values were related to that of the growth medium [214–217]. 3.5.8. Documents In the Amerithrax case, the isotopic analysis of the cellulose of the envelopes used to mail the spores was undertaken

153

[210,211]. However, the results showed limited discrimination between envelopes. Van Es et al. reported the discrimination of 21 out of 25 paper samples coming from the European market, based on their d13 C, d18 O and d2 H values [218]. A large study on the d13 C value of office paper was published in trifold by Jones et al. [219–221]. They analysed 125 samples from Australia and New Zealand and noticed a relationship between the carbon isotope ratio and the region of production of the papers. The intra and intervariability of reams of papers coming from seven brands were evaluated. The influence of the manufacturing process of paper on the d13 C value of cellulose was also studied. Ink and toner particles from printing and photocopying processes showed to modify the d13 C value of the paper. The validation of the method was reported. 3.5.9. Poisons Some authors started to get interested in the differentiation of sources of poisons, such as sodium and potassium cyanide (NaCN and KCN). Tea et al. measured the d13 C and d15 N values of these substances and found well dispersed values with small overlap. However, no further consideration is provided on the ability of the technique to discriminate the specimens. Investigations on the extraction of these poisons from matrices, such as orange juice, yoghurt drink and medicine, was also undertaken [222]. Additional data on 25 NaCN samples and 40 KCN samples, coming from 14 different suppliers, were further published by Kreuzer et al. [223]. Castor seeds and their derived products, including ricin, were also analysed by IRMS [224]. 307 samples of castor seeds were collected from worldwide locations. The d15 N values of extracted ricin and source seeds were very similar, indicating that it could be used to exclude potential source seeds. The isotopic profiles of ricin samples were also compared against each other in order to match samples. Furthermore, the d2 H values of castor oil could be exploited to infer the geographical origin of castor seeds. 3.5.10. Miscellaneous Using IRMS in the context of a safe burglary case, the isotopic composition of a safe filling material was compared to the material recovered in a bag of a suspect [225]. Both materials could not be differentiated. IRMS was used to infer the geographical origin of a carbonate rock used to replace a stolen volume of nickel metal [226]. The isotopic data supported the hypothesis that the rock originated from Israel rather than South Africa. Michalski et al. investigated the reason for the high nitrate concentration found in the Main Lake depression of the Nevada desert that poisoned 71 wild horses [227]. Isotopic analysis of the nitrate contained in the lake did not support the dumping of synthetic urea into water, but rather horse’s manure, followed high evaporative conditions, as the source of water nitrification. The analysis of acid scavenger compounds used to stabilise nerve agents was reported by Moran et al. [228]. The isotopic profile of 22 samples coming from 3 different suppliers and from inventories of chemical laboratories could be used to distinguish between samples and establish a link with potential precursors. 4. Conclusion The review of the different fields of applications not only showed the ability of IRMS to discriminate samples of the same chemical nature, but also its possibilities to answer the various questions behind the notion of source. The upcoming challenges do no longer reside in multiplying the demonstrations of discrimination capacities of IRMS, but rather in deepening the knowledge already gathered and improving the understanding of the limitations of the technology in a forensic context. In order to

154

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

strengthen current knowledge, a special emphasis should be put on the collection of data on intravariability and the definition of the notion of source, which is itself directly connected with the sampling. Moreover, further studies evaluating factors that may influence the isotopic profile are needed. These essential elements should allow a better interpretation of the results and should elevate our awareness of the limits and possibilities of the technique. The use of databases is of particular interest in the forensic community and has been at the heart of many discussions. As isotopic results are reported on an international reference scale, the isotopic measurement ‘‘system’’ is perfectly compatible with the use of databases and offers interesting possibilities for collaborations on a national or international level. Thus, different laboratories could therefore contribute to the construction and update of a database. Interactive databases in climatology, hydrology and food adulteration show that sharing isotopic data on a national or international level is feasible. However, some significant aspects need first to be addressed and have been discussed in [57]. Furthermore, the implementation of a database is never trivial. Defining the purpose of the database and how the information will be exploited are necessary and should be made clear. The great efforts behind the use of a database (supplying it with data, keeping it up-to-date, sharing, transmitting and using the information) may be dissuasive. Nevertheless, even without any database, this should not prevent us from exploiting the great advantage of IRMS over other techniques (the production of data comparable on an international scale) to exchange and share data between laboratories.

References [1] S. Benson, C. Lennard, P. Maynard, C. Roux, Forensic applications of isotope ratio mass spectrometry – a review, Forensic Sci. Int. 157 (1) (2006) 1–22. [2] W. Meier-Augenstein, R.H. Liu, Forensic applications of isotope ratio mass spectrometry, in: J. Yinon (Ed.), Advances in Forensic Applications of Mass Spectrometry, CRC Press, 2004, pp. 149–180. [3] W. Meier-Augenstein, Stable isotope fingerprinting – chemical element ‘‘DNA’’? in: T. Thompson, S. Black (Eds.), Forensic Human Identification, CRC Press, Boca Raton, FL, 2007, pp. 29–53. [4] W. Meier-Augenstein, Stable Isotope Forensics: An Introduction to the Forensic Application of Stable Isotope Analysis, John Wiley & Sons, 2010. [5] L. Chesson, B.J. Tipple, J.D. Howa, G.J. Bowen, J.E. Barnette, T.E. Cerling, J.R. Ehleringer, Stable Isotopes in Forensics Applications, in: Treatise on Geochemistry, second ed., Elsevier, 2014, pp. 285–317. [6] Q.Y. Kwan, Inference of identity of source, PhD Thesis, University of California, 1977. [7] A. Rossmann, Determination of stable isotope ratios in food analysis, Food Rev. Int. 17 (3) (2001) 347–381. [8] S.D. Kelly, Using stable isotope ratio mass spectrometry (IRMS) in food authentication and traceability, in: M. Lees (Ed.), Food Authenticity and Traceability, Woodhead Publishing, Cambridge, 2003, pp. 156–183. [9] S. Kelly, Tracing the geographical origin of food: the application of multi-element and multi-isotope analysis, Trends Food Sci. Tech. 16 (2005) 555–567. [10] H. Forstel, The natural fingerprint of stable isotopes – use of IRMS to test food authenticity, Anal. Bioanal. Chem. 388 (3) (2007) 541–544. [11] A. Gonzalvez, S. Armenta, M. de la Guardia, Trace-element composition and stable-isotope ratio for discrimination of foods with protected designation of origin, TRAC-Trend Anal. Chem. 28 (11) (2009) 1295–1311. [12] S. Primrose, M. Woolfe, S. Rollinson, Food forensics: methods for determining the authenticity of foodstuffs, Trends Food Sci. Tech. 21 (12) (2010) 582–590. [13] M. Boner, H. Fo¨rstel, Stable isotope variation as a tool to trace the authenticity of beef, Anal. Bioanal. Chem. 378 (2) (2004) 301–310. [14] R. Nakashita, Y. Suzuki, F. Akamatsu, Y. Iizumi, T. Korenaga, Y. Chikaraishi, Stable carbon, nitrogen, and oxygen isotope analysis as a potential tool for verifying geographical origin of beef, Anal. Chim. Acta 617 (1-2) (2008) 148–152. [15] J.P. Jasper, Pharmaceutical security: using stable isotopes to autenticate pharmaceutical materials, Tablets Capsules 2 (3) (2004) 37–42. [16] R. Santamaria-Fernandez, R. Hearn, J.-C. Wolff, Detection of counterfeit antiviral drug Heptodin and classification of counterfeits using isotope amount ratio measurements by multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) and isotope ratio mass spectrometry (IRMS), Sci. Justice 49 (2) (2009) 102–106. [17] M.J. DeNiro, S. Epstein, Influence of diet on the distribution of carbon isotopes in animals, Geochim. Cosmochim. Acta 42 (5) (1978) 495–506.

[18] M.J. DeNiro, S. Epstein, Influence of diet on the distribution of nitrogen isotopes in animals, Geochim. Cosmochim. Acta 45 (3) (1981) 341–351. [19] M.J. Schoeninger, M.J. DeNiro, Nitrogen and carbon isotopic composition of bone collagen from marine and terrestrial animals, Geochim. Cosmochim. Acta 48 (1984) 625–639. [20] C.P. Chamberlain, J.D. Blum, R.T. Holmes, X. Feng, T.W. Sherry, G.R. Graves, The use of isotope tracers for identifying populations of migratory birds, Oecologia 109 (1997) 132–141. [21] K.A. Hobson, Tracing origins and migration of wildlife using stable isotopes: a review, Oecologia 120 (1999) 314–326. [22] K.A. Hobson, G.J. Bowen, L.I. Wassenaar, Y. Ferrand, H. Lormee, Using stable hydrogen and oxygen isotope measurements of feathers to infer geographical origins of migrating European birds, Oecologia 141 (3) (2004) 477–488. [23] T.E. Cerling, G. Wittemyer, H.B. Rasmussen, F. Vollrath, C.E. Cerling, T.J. Robinson, I. Douglas-Hamilton, Stable isotopes in elephant hair document migration patterns and diet changes, Proc. Natl. Acad. Sci. U. S. A. 103 (2) (2006) 371–373. [24] A. Kelly, R. Thompson, J. Newton, Stable hydrogen isotope analysis as a method to identify illegally trapped songbirds, Sci. Justice 48 (2) (2008) 67–70. [25] J.A. Seminoff, S.R. Benson, K.E. Arthur, T. Eguchi, P.H. Dutton, R.F. Tapilatu, B.N. Popp, Stable isotope tracking of endangered sea turtles: validation with satellite telemetry and d15N analysis of amino acids, PLoS ONE 7 (5) (2012) e37403. [26] G.J. Bowen, L.I. Wassenaar, K.A. Hobson, Global application of stable hydrogen and oxygen isotopes to wildlife forensics, Oecologia 143 (3) (2005) 337–348. [27] V.P. O’Malley, T.A. Abrajano Jr., J. Hellou, Determination of the 13 C/12 C ratios of individual PAH from environmental samples: can PAH sources be apportioned? Org. Geochem. 21 (6-7) (1994) 809–822. [28] R.R. Harrington, S.R. Poulson, J.I. Drever, P.J.S. Colberg, E.F. Kelly, Carbon isotope systematics of monoaromatic hydrocarbons: vaporization and adsorption experiments, Org. Geochem. 30 (1999) 765–775. [29] Z. Wang, M. Fingas, D.S. Page, Review: oil spill identification, J. Chromatogr. A 843 (1999) 369–411. [30] H. Budzinski, L. Maze´as, K. Le Menach, d13 C analysis of PAH: a new dimension in source assessment studies, Chimia 57 (1-2) (2003) 41–43. [31] T.J. Boyd, R.B. Coffin, Use of stable carbon isotopes and multivariate statistics to source-apportion fuel hydrocarbons, Environ. Res. Eng. Manage. 4 (30) (2004) 28–35. [32] T.J. Boyd, C.L. Osburn, K.J. Johnson, K.B. Birgl, R.B. Coffin, Compound-specific isotope analysis coupled with multivariate statistics to source-apportion hydrocarbon mixtures, Environ. Sci. Technol. 40 (6) (2006) 1916–1924. [33] W.J. Shin, S.-W. Lee, S.-Y. Heo, K.-S. Lee, Stable isotope fingerprinting for identification of the methyl tert-butyl ether (MTBE) manufacturer, Environ. Forensics 14 (1) (2013) 36–41. [34] B.J. Smallwood, R.P. Philp, T.W. Burgoyne, The use of stable isotopes to differentiate specific source markers for MTBE, Environ. Forensics 2 (2001) 2215–2221. [35] Y. Wang, Y. Huang, Hydrogen isotope fractionation of low molecular weight nalkanes during progressive vaporization, Org. Geochem. 32 (2001) 991–998. [36] S.R. Silva, P.B. Ging, R.W. Lee, J.C. Ebbert, A.J. Tesoriero, E.L. Inkpen, Forensic applications of nitrogen and oxygen isotopes in tracing nitrate sources in urban environments, Environ. Forensics 3 (2002) 125–130. [37] T. Kuder, P. Philp, J. Allen, Effects of volatilization on carbon and hydrogen isotope ratios of MTBE, Environ. Sci. Technol. 43 (6) (2009) 1763–1768. [38] B. Carpentier, P. Ungerer, K.I.C. Magnier, J.P. Courcy, A.Y. Huc, Molecular and isotopic fractionation of light hydrocarbons between oil and gas phases, Org. Geochem. 24 (12) (1996) 1115–1139. [39] L. Mansuy, P.R. Philp, J. Allen, Source identification of oil spills based on the isotopic composition of individual components in weathered oil samples, Environ. Sci. Technol. 31 (1997) 3417–3425. [40] E. Diegor, T. Abrajano, T. Patel, L. Stehmeier, J. Gow, L. Winsor, Biodegradation of aromatic hydrocarbons: microbial and isotopic studies, J. Conf. Abst. 5 (2) (2000) 349–350. [41] B. Morasch, H.H. Richnow, B. Schink, A. Vieth, R.U. Meckenstock, Carbon and hydrogen stable isotope fractionation during aerobic bacterial degradation of aromatic hydrocarbons, Appl. Environ. Microb. 68 (10) (2002) 5191–5194. [42] Y. Li, Y. Xiong, W. Yang, Y. Xie, S. Li, Y. Sun, Compound-specific stable carbon isotopic composition of petroleum hydrocarbons as a tool for tracing the source of oil spills, Mar. Pollut. Bull. 58 (1) (2009) 114–117. [43] W.J. Shin, K.S. Lee, Carbon isotope fractionation of benzene and toluene by progressive evaporation, Rapid Commun. Mass Spectrom. 24 (11) (2010) 1636– 1640. [44] T.C. Schmidt, L. Zwank, M. Elsner, M. Berg, R.U. Meckenstock, S.B. Haderlein, Compound-specific stable isotope analysis of organic contaminants in natural environments: a critical review of the state of the art, prospects and future challenges, Anal. Bioanal. Chem. 378 (2) (2004) 283–300. [45] R.P. Philp, The emergence of stable isotopes in environmental and forensic geochemistry studies: a review, Environ. Chem. Lett. 5 (2007) 57–66. [46] M. Becchi, R. Aguilera, Y. Farizon, M.M. Flament, H. Casabianca, P. James, Gas chromatography/combustion/isotope-ratio mass spectrometry analysis of urinary steroids to detect misuse of testosterone in sport, Rapid. Commun. Mass Spectrom. 8 (4) (1994) 304–308. [47] A.T. Cawley, U. Flenker, The application of carbon isotope ratio mass spectrometry to doping control, J Mass Spectrom 43 (7) (2008) 854–864. [48] U. Flenker, U. Gu¨ntner, W. Scha¨nzer, d13 C-values of endogenous urinary steroids, Steroids 73 (4) (2008) 408–416. [49] T. Piper, U. Mareck, H. Geyer, U. Flenker, M. Thevis, P. Platen, W. Schanzer, Determination of 13 C/12 C ratios of endogenous urinary steroids: method validation, reference population and application to doping control purposes, Rapid Commun. Mass Spectrom. 22 (14) (2008) 2161–2175.

N. Gentile et al. / Forensic Science International 251 (2015) 139–158 [50] A.T. Cawley, G.J. Trout, R. Kazlauskas, C.J. Howe, A.V. George, Carbon isotope ratio (d13 C) values of urinary steroids for doping control in sport, Steroids 74 (3) (2009) 379–392. [51] T. Piper, U. Flenker, U. Mareck, W. Schanzer, 13 C/12 C ratios of endogenous urinary steroids investigated for doping control purposes, Drug Test Anal. 1 (2) (2009) 65–72. [52] C. Saudan, C. Emery, F. Marclay, E. Strahm, P. Mangin, M. Saugy, Validation and performance comparison of two carbon isotope ratio methods to control the misuse of androgens in humans, J. Chromatogr. B 877 (23) (2009) 2321– 2329. [53] A.T. Cawley, M. Collins, R. Kazlauskas, D.J. Handelsman, R. Heywood, M. Longworth, A. Arenas-Queralt, Stable isotope ratio profiling of testosterone preparations, Drug Test Anal. 2 (11-12) (2010) 557–567. [54] L. Brooker, A. Cawley, J. Drury, C. Edey, N. Hasick, C. Goebel, Stable carbon isotope ratio profiling of illicit testosterone preparations-domestic and international seizures, Drug Test Anal. 6 (10) (2014) 996–1001. [55] Court of Arbitration for Sport, Arbitration CAS 2007/A/1394 Floyd Landis v. USADA, award of 30 June, 2008. [56] T. Piper, C. Emery, M. Saugy, Recent developments in the use of isotope ratio mass spectrometry in sports drug testing, Anal. Bioanal. Chem. 401 (2) (2011) 433–447. [57] N. Gentile, Exploration of the contribution of isotope ratio mass spectrometry to the investigation of explosives: A study of black powders and ammonium nitrate, PhD Thesis, University of Lausanne, School of Criminal Justice, 2014. [58] J.H. Liu, W.-F. Lin, M.P. Fitzgerald, S.C. Saxena, Y.N. Shieh, Possible characterization of samples of cannabis sativa L. by their carbon isotopic distributions, J. Forensic Sci. 24 (1979) 814–816. [59] E.M. Galimov, V.S. Sevastyanov, E.V. Kulbachevskaya, A.A. Golyavin, Isotope ratio mass spectrometry: d13 C and d15 N analysis for tracing the origin of illicit drugs, Rapid Commun. Mass Spectrom. 19 (10) (2005) 1213–1216. [60] E.K. Shibuya, J.E. Souza Sarkis, O.N. Neto, M.Z. Moreira, R.L. Victoria, Sourcing Brazilian marijuana by applying IRMS analysis to seized samples, Forensic Sci. Int. 160 (1) (2006) 35–43. [61] E.K. Shibuya, J.E. Sarkis, O. Negrini-Neto, L.A. Martinelli, Carbon and nitrogen stable isotopes as indicative of geographical origin of marijuana samples seized in the city of Sa˜o Paulo (Brazil), Forensic Sci. Int. 167 (1) (2007) 8–15. [62] E.K. Shibuya, J.E. Sarkis, O. Negrini-Neto, J.P.H.B. Ometto, Multivariate classification based on chemical and stable isotopic profiles in sourcing the origin of marijuana samples seized in Brazil, J. Braz. Chem. Soc. 18 (1) (2007) 205–214. [63] J.B. West, J.M. Hurley, J.R. Ehleringer, Stable isotope ratios of marijuana. I. Carbon and nitrogen stable isotopes describe growth conditions, J. Forensic Sci. 54 (1) (2009) 84–89. [64] A.L. Booth, M.J. Wooller, T. Howe, N. Haubenstock, Tracing geographic and temporal trafficking patterns for marijuana in Alaska using stable isotopes (C, N, O and H), Forensic Sci. Int. 202 (1–3) (2010) 45–53. [65] J.M. Hurley, J.B. West, J.R. Ehleringer, Stable isotope models to predict geographic origin and cultivation conditions of marijuana, Sci. Justice 50 (2) (2010) 86–93. [66] J.M. Hurley, J.B. West, J.R. Ehleringer, Tracing retail cannabis in the United States: geographic origin and cultivation patterns, Int. J. Drug Policy 21 (3) (2010) 222– 228. [67] T.M. Denton, S. Schmidt, C. Critchley, G.R. Stewart, Natural abundance of stable carbon and nitrogen isotopes in Cannabis sativa reflects growth conditions, Aust. J. Plant Physiol. 28 (10) (2001) 1005–1012. [68] Z. Muccio, C. Wo¨ckel, Y. An, G.P. Jackson, Comparison of bulk and compound specific d13 C isotope ratio analyses for the discrimination between cannabis samples, J. Forensic Sci. 57 (3) (2012) 757–764. [69] Forensic Isotope Ratio Mass Spectrometry, IRMS evidence presented in Court, FIRMS Newsletter 1(3) (2003). [70] J.R. Ehleringer, D.A. Cooper, M.J. Lott, C.S. Cook, Geo-location of heroin and cocaine by stable isotope ratios, Forensic Sci. Int. 106 (1999) 27–35. [71] J.R. Ehleringer, J.F. Casale, M.J. Lott, V.L. Ford, Tracing the geographical origin of cocaine, Nature 408 (6810) (2000) 311–312. [72] S. Sewenig, S. Fichtner, T. Holdermann, G. Fritschi, H. Neumann, Determination of d13 C and d15 N values of cocaine from a big seizure in Germany by stable isotope ratio mass spectrometry, Isotopes Environ. Health Stud. 43 (4) (2007) 275–280. [73] Finnigan MAT, 15 N /14 N and 13 C/12 C by EA-IRMS. Forensic studies using the ConFlo II interface, Application Flash Report No. 15 12/95 PL 0/1177, 1995. [74] E. Ihle, H.-L. Schmidt, Multielement isotope analysis on drugs of abuse: possibility for their origin assignment, Isotopes Environ. Health Stud. 32 (1996) 226– 228. [75] Z. Muccio, G.P. Jackson, Simultaneous identification and d13 C classification of drugs using GC with concurrent single quadrupole and isotope ratio mass spectrometers, J. Forensic Sci. 56 (suppl. 1) (2011) S203–209. [76] J.F. Casale, J.R. Ehleringer, D.R. Morello, M.J. Lott, Isotopic fractionation of carbon and nitrogen during the illicit processing of cocaine and heroin in South America, J. Forensic Sci. 50 (6) (2005) 1315–1321. [77] M. Desage, R. Guilluy, J.L. Brazier, Gas chromatography with mass spectrometry or isotope-ratio mass spectrometry in studying the geographical origin of heroin, Anal. Chim. Acta 247 (1991) 249–254. [78] F.A. Idoine, J.F. Carter, R. Sleeman, Bulk and compound-specific isotopic characterisation of illicit heroin and cling film, Rapid Commun. Mass Spectrom. 19 (22) (2005) 3207–3215. [79] D. Zhang, W. Sun, Z. Yuan, H. Ju, X. Shi, C. Wang, Origin differentiation of heroin sample and its acetylating agent with 13 C isotope ratio mass spectrometry, Eur. J. Mass Spectrom. 11 (3) (2005) 277–285.

155

[80] J.F. Casale, E. Casale, M. Collins, D.R. Morello, S. Cathapermal, S. Panicker, Stable isotope analyses of heroin seized from the merchant vessel Pong Su, J. Forensic Sci. 51 (3) (2006) 603–606. [81] F. Besacier, R. Guilluy, J.L. Brazier, H. Chaudron-Thozet, J. Girard, A. Lamotte, Isotopic analysis of 13 C as a tool for comparison and origin assignment of seized heroin samples, J. Forensic Sci. 42 (3) (1997) 429–433. [82] S. Dautraix, R. Guilluy, H. Chaudron-Thozet, J.L. Brazier, A. Lamotte, 13 C isotopic analysis of an acetaminophen and diacetylmorphine mixture, J. Chromatogr. A 756 (1996) 203–210. [83] F. Besacier, H. Chaudron-Thozet, M. Rousseau-Tsangaris, J. Girard, A. Lamotte, Comparative chemical analyses of drug samples: general approach and application to heroin, Forensic Sci. Int. 85 (2) (1997) 113–125. [84] F. Besacier, H. Chaudron-Thozet, F. Lascaux, M. Rousseau-Tsangaris, Application du couplage chromatographie gazeuse-spectrome´trie de masse isotopique de l’azote a` l’analyse d’e´chantillons de drogues, Analusis 27 (3) (1999) 213–217. [85] S.A. Phillips, S. Doyle, S. Mountford, Proceedings of the Forensic Isotope Ratio Mass Spectrometry (FIRMS) workshop, 2003. [86] J.F. Carter, R. Sleeman, J.C. Hill, F. Idoine, E.L. Titterton, Isotope ratio mass spectrometry as a tool for forensic investigation (examples from recent studies), Sci. Justice 45 (3) (2005) 141–149. [87] F. Mas, B. Beemsterboer, A.C. Veltkamp, A.M.A. Verweij, Determination of ‘common-batch’ members in a set of confiscated 3,4-(methylendioxy)-methylamphetamine samples by measuring the natural isotope abundances: a preliminary study, Forensic Sci. Int. 71 (1995) 225–231. [88] J.F. Carter, E.L. Titterton, M. Murray, R. Sleeman, Isotopic characterisation of 3,4methylenedioxyamphetamine and 3,4-methylenedioxymethylamphetamine (ecstasy), Analyst 127 (6) (2002) 830–833. [89] A. de Korompay, J.C. Hill, J.F. Carter, N. Nic Daeid, R. Sleeman, Supported liquid– liquid extraction of the active ingredient (3,4-methylenedioxymethylamphetamine) from ecstasy tablets for isotopic analysis, J. Chromatogr. A 1178 (1-2) (2008) 1–8. [90] F. Palhol, M. Chabrillat, N. Naulet, The use of GC-C-IRMS analyses for linking seizures of ecstasy tablets, in: Poster presented at the Network Developing Forensic Applications of Stable Isotope Mass Spectrometry, Kent, U. K., 16–17 September, 2002. [91] F. Palhol, C. Lamoureux, N. Naulet, 15 N isotopic analyses: a powerful tool to establish links between seized 3,4-methylenedioxymethamphetamine (MDMA) tablets, Anal. Bioanal. Chem. 376 (4) (2003) 486–490. [92] J.F. Carter, E.L. Titterton, H. Grant, R. Sleeman, Isotopic changes during the synthesis of amphetamines, Chem. Commun. 8 (21) (2002) 2590–2591. [93] I. Billault, F. Courant, L. Pasquereau, S. Derrien, R.J. Robins, N. Naulet, Correlation between the synthetic origin of methamphetamine samples and their 15 N and 13 C stable isotope ratios, Anal. Chim. Acta 593 (1) (2007) 20–29. [94] H.A. Buchanan, N. Nic Daeid, W. Meier-Augenstein, H.F. Kemp, W.J. Kerr, M. Middleditch, Emerging use of isotope ratio mass spectrometry as a tool for discrimination of 3,4-methylenedioxymethamphetamine by synthetic route, Anal. Chem. 80 (9) (2008) 3350–3356. [95] H.A. Buchanan, N. Nic Daeid, W.J. Kerr, J.F. Carter, J.C. Hill, Role of five synthetic reaction conditions on the stable isotopic composition of 3,4-methylenedioxymethamphetamine, Anal. Chem. 82 (13) (2010) 5484–5489. [96] F. Palhol, C. Lamoureux, M. Chabrillat, N. Naulet, 15 N/14 N isotopic ratio and statistical analysis: an efficient way of linking seized Ecstasy tablets, Anal. Chim. Acta 510 (2004) 1–8. [97] H.A. Buchanan, W.J. Kerr, W. Meier-Augenstein, N. Nic Daeid, Organic impurities, stable isotopes, or both: a comparison of instrumental and pattern recognition techniques for the profiling of 3,4-methylenedioxymethamphetamine, Anal. Methods 3 (2011) 2279–2288. [98] Forensic Isotope Ratio Mass Spectrometry, IRMS evidence used in Court, FIRMS Newsletter 1(2) (2003). [99] D. Wakelin, S. Doyle, C. Andrews, S. Mountford, N. Nic Daeid, Network developing forensic applications of stable isotope ratio mass spectrometry conference 2005, Sci. Justice 48 (2) (2008) 79–90. [100] N. Kurashima, Y. Makino, S. Sekita, Y. Urano, T. Nagano, Determination of origin of ephedrine used as precursor for illicit methamphetamine by carbon and nitrogen stable isotope ratio analysis, Anal. Chem. 76 (14) (2004) 4233–4236. [101] N. Kurashima, Y. Makino, Y. Urano, K. Sanuki, Y. Ikehara, T. Nagano, Use of stable isotope ratios for profiling of industrial ephedrine samples: application of hydrogen isotope ratios in combination with carbon and nitrogen, Forensic Sci. Int. 189 (1-3) (2009) 14–18. [102] M. Collins, A.T. Cawley, A.C. Heagney, L. Kissane, J. Robertson, H. Salouros, d13 C, d15 N and d2 H isotope ratio mass spectrometry of ephedrine and pseudoephedrine: application to methylamphetamine profiling, Rapid Commun. Mass Spectrom. 23 (13) (2009) 2003–2010. [103] Y. Makino, Y. Urano, T. Nagano, Investigation of the origin of ephedrine and methamphetamine by stable isotope ratio mass spectrometry: a Japanese experience, B Narcotics 57 (1–2) (2005) 63–78. [104] S. Schneiders, T. Holdermann, R. Dahlenburg, Comparative analysis of 1-phenyl2-propanone (P2P), an amphetamine-type stimulant precursor, using stable isotope ratio mass spectrometry, Sci. Justice 49 (2) (2009) 94–101. [105] Y.T. Iwata, K. Kuwayama, K. Tsujikawa, H. Miyaguchi, T. Kanamori, H. Inoue, Seized methamphetamine samples with unique profiles of stable nitrogen isotopic composition documented by stable isotope ratio mass spectrometry, Forensic Toxicol. 28 (2010) 119–123. [106] G.E. David, A. Coxon, R.D. Frew, A.R. Hayman, Isotope fractionation during precipitation of methamphetamine HCl and discrimination of seized forensic samples, Forensic Sci. Int. 200 (1–3) (2010) 123–129.

156

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

[107] G.E. David, D.B. Hibbert, R.D. Frew, A.R. Hayman, Significant determinants of isotope composition during HI/Pred synthesis of methamphetamine, Aust. J. Chem. 63 (1) (2010) 22–29. [108] H. Salouros, M. Collins, A. Cawley, M. Longworth, Methylamphetamine synthesis: does an alteration in synthesis conditions affect the d13 C, d15 N and d2 H stable isotope ratio values of the product? Drug Test. Anal. 4 (5) (2012) 330–336. [109] S.G. Toske, D.R. Morello, J.M. Berger, E.R. Vazquez, The use of d13 C isotope ratio mass spectrometry for methamphetamine profiling: Comparison of ephedrine and pseudoephedrine-based samples to P2P-based samples, Forensic Sci. Int. 234 (2014) 1–6. [110] N. Nic Daeid, S. Jayamana, W.J. Kerr, W. Meier-Augenstein, H.F. Kemp, Influence of precursor solvent extraction on stable isotope signatures of methylamphetamine prepared from over-the-counter medicines using the Moscow and Hypophosphorous routes, Anal. Bioanal. Chem. 405 (9) (2013) 2931–2941. [111] Y.T. Iwata, K. Kuwayama, K. Tsujikawa, H. Miyaguchi, T. Kanamori, H. Inoue, Evaluation method for linking methamphetamine seizures using stable carbon and nitrogen isotopic compositions: a complementary study with impurity profiling, Rapid Commun. Mass Spectrom. 22 (23) (2008) 3816–3822. [112] K. Tsujikawa, T. Mikuma, K. Kuwayama, H. Miyaguchi, T. Kanamori, Y.T. Iwata, H. Inoue, Profiling of seized methamphetamine putatively synthesized by reductive amination of 1-phenyl-2-propanone, Forensic Toxicol. 30 (2012) 70–75. [113] M. Collins, H. Salouros, A.T. Cawley, J. Robertson, A.C. Heagney, A. Arenas-Queralt, d13 C and d2 H isotope ratios in amphetamine synthesized from benzaldehyde and nitroethane, Rapid Commun. Mass Spectrom. 24 (11) (2010) 1653–1658. [114] N. Nic Daeid, W. Meier-Augenstein, H.F. Kemp, O.B. Sutcliffe, Using isotopic fractionation to link precursor to product in the synthesis of ()-mephedrone: a new tool for combating ‘‘legal high’’ drugs, Anal. Chem. 84 (20) (2012) 8691– 8696. [115] F. Marclay, D. Pazos, O. Delemont, P. Esseiva, C. Saudan, Potential of IRMS technology for tracing gamma-butyrolactone (GBL), Forensic Sci. Int. 198 (1) (2010) 46–52. [116] D. Pazos, P. Giannasi, Q. Rossy, P. Esseiva, Combining Internet monitoring processes, packaging and isotopic analyses to determine the market structure: example of Gamma Butyrolactone, Forensic Sci. Int. 230 (1-3) (2013) 29–36. [117] C. Saudan, M. Augsburger, P. Mangin, M. Saugy, Carbon isotopic ratio analysis by gas chromatography/combustion/isotope ratio mass spectrometry for the detection of gamma-hydroxybutyric acid (GHB) administration to humans, Rapid Commun. Mass Spectrom. 21 (24) (2007) 3956–3962. [118] F. Marclay, C. Saudan, J. Vienne, M. Tafti, M. Saugy, Source inference of exogenous gamma-hydroxybutyric acid (GHB) administered to humans by means of carbon isotopic ratio analysis: novel perspectives regarding forensic investigation and intelligence issues, Anal. Bioanal. Chem. 400 (4) (2011) 1105–1112. [119] M.A. Katzenberg, H.R. Krouse, Application of stable isotope variation in human tissues to problems in identification, J. Can. Soc. Forensic Sci. 22 (1) (1989) 7–19. [120] J.W. O’Reilly, The ‘‘Adam’’ Case, London, in: T.J.T. Thomson, S.M. Black (Eds.), Forensic Human Identification – An Introduction, CRC Press, Boca Raton, FL, 2007, pp. 473–484, Ch. 27. [121] E. Rauch, S. Rummel, C. Lehn, A. Bu¨ttner, Origin assignment of unidentified corpses by use of stable isotope ratios of light (bio-) and heavy (geo-) elements – a case report, Forensic Sci. Int. 168 (2–3) (2007) 215–218. [122] W. Meier-Augenstein, I. Fraser, Forensic isotope analysis leads to identification of a mutilated murder victim, Sci. Justice 48 (3) (2008) 153–159. [123] C.D. Kennedy, G.J. Bowen, J.R. Ehleringer, Temporal variation of oxygen isotope ratios d18 O in drinking water: Implications for specifying location of origin with human scalp hair, Forensic Sci. Int. 208 (1-3) (2011) 156–166. [124] A. Longinelli, Oxygen isotopes in mammal bone phosphate: a new tool for paleohydrological and paleoclimatological research, Geochim. Cosmochim. Acta 48 (1984) 385–390. [125] J. Lee-Thorp, M. Sponheimer, Three case studies used to reassess the reliability of fossil bone and enamel isotope signals for paleodietary studies, J. Anthropol. Archaeol. (2003) 208–216. [126] Z.D. Sharp, V. Atudorei, H.O. Panarello, J. Fernandez, C. Douthitt, Hydrogen isotope systematics of hair: archeological and forensic applications, J. Archeol. Sci. 30 (2003) 1709–1716. [127] R. Bianucci, M. Jeziorska, R. Lallo, G. Mattutino, M. Massimelli, G. Phillips, O. Appenzeller, A pre-Hispanic head, PLoS ONE 3 (4) (2008) e2053. [128] G.J. Bowen, Isoscapes: spatial pattern in isotopic biogeochemistry, Annu. Rev. Earth Plant Sci. 38 (2010) 161–197. [129] West Lab, Isoscapes – Understanding the spatial component of Earth system isotope ratios, https://sites.google.com/site/westlabgroup/isoscapes-home (accessed 19.05.11). [130] J.R. Ehleringer, G.J. Bowen, L.A. Chesson, A.G. West, D.W. Podlesak, T.E. Cerling, Hydrogen and oxygen isotope ratios in human hair are related to geography, Proc. Natl. Acad. Sci. U. S. A. 105 (8) (2008) 2788–2793. [131] G. Van der Veer, S. Voerkelius, G. Lorentz, G. Heiss, J.A. Hoogewerff, Spatial interpretation of the deuterium and oxygen-18 composition of global precipitation using temperature as ancillary variable, J. Geochem. Explor. 101 (2009) 175–184. [132] C. Lehn, M. Graw, Wie viel Regionalita¨t steckt in Ko¨rpergewebe, Rechtsmedizin 2 (2012) 99–105. [133] T.C. O’Connell, R.E.M. Hedges, Investigations into the effect of diet on modern human hair isotopic values, Am. J. Phys. Anthropol. 108 (4) (1999) 409–425. [134] T.C. O’Connell, R.E.M. Hedges, Isotopic comparison of hair, nail and bone: modern analyses, J. Archeol. Sci. 28 (2001) 1247–1255. [135] R. Bol, C. Pflieger, Stable isotope (13 C, 15 N and 34 S) analysis of the hair of modern humans and their domestic animals, Rapid Commun. Mass Spectrom. 16 (23) (2002) 2195–2200.

[136] B.T. Fuller, J.L. Fuller, N.E. Sage, D.A. Harris, T.C. O’Connell, R.E.M. Hedges, Nitrogen balance and d15 N: why you’re not what you eat during nutritional stress, Rapid Commun. Mass Spectrom. 19 (18) (2005) 2497–2506. [137] K.J. Petzke, H. Boeing, C.C. Metges, Choice of dietary protein of vegetarians and omnivores is reflected in their hair protein 13 C and 15 N abundance, Rapid Commun. Mass Spectrom. 19 (11) (2005) 1392–1400. [138] I. Fraser, W. Meier-Augenstein, R.M. Kalin, The role of stable isotopes in human identification: a longitudinal study into the variability of isotopic signals in human hair and nails, Rapid Commun. Mass Spectrom. 20 (7) (2006) 1109–1116. [139] R. Bol, J. Marsh, T.H.E. Heaton, Multiple stable isotope (18 O, 13 C, 15 N and 34 SC) analysis of human hair to identify the recent migrants in a rural community in SW England, Rapid Commun. Mass Spectrom. 21 (18) (2007) 2951–2954. [140] I. Fraser, W. Meier-Augenstein, Stable 2 H isotope analysis of modern-day human hair and nails can aid forensic human identification, Rapid Commun. Mass Spectrom. 21 (20) (2007) 3279–3285. [141] D.M. O’Brien, M.J. Wooller, Tracking human travel using stable oxygen and hydrogen isotope analyses of hair and urine, Rapid Commun. Mass Spectrom. 21 (15) (2007) 2422–2430. [142] I. Fraser, W. Meier-Augenstein, R.M. Kalin, Stable isotope analysis of human hair and nail samples: the effects of storage on samples, J. Forensic Sci. 53 (1) (2008) 95–99. [143] E. Mu¨tzel Rauch, C. Lehn, O. Peschel, S. Ho¨lzl, A. Rossmann, Assignment of unknown persons to their geographical origin by determination of stable isotopes in hair samples, Int. J. Legal Med. 123 (1) (2009) 35–40. [144] A.H. Thompson, L.A. Chesson, D.W. Podlesak, G.J. Bowen, T.E. Cerling, J.R. Ehleringer, Stable isotope analysis of modern human hair collected from Asia (China, India, Mongolia, and Pakistan), Am. J. Phys. Anthropol. 141 (3) (2010) 440–451. [145] C. Lehn, E. Mu¨tzel, A. Rossmann, Multi-element stable isotope analysis of H, C, N and S in hair and nails of contemporary human remains, Int. J. Legal Med. 125 (5) (2011) 695–706. [146] W. Meier-Augenstein, M.M.G. Chartrand, H.F. Kemp, G. St-Jean, An inter-laboratory comparative study into sample preparation for both reproducible and repeatable forensic 2 H isotope analysis of human hair by continuous flow isotope ratio mass spectrometry, Rapid Commun. Mass Spectrom. 25 (21) (2011) 3331–3338. [147] K. Alkass, H. Saitoh, B. Buchholz, S. Bernard, G. Holmlund, D. Senn, K. Spalding, H. Druid, Analysis of radiocarbon, stable isotopes and dna in teeth to facilitate identification of unknown decedents, PLoS ONE 8 (7) (2013) e69597. [148] L.S. Bell, J.A. Lee-Thorp, K. Dobney, Mapping human movement using stable oxygen isotopic ratio mass spectrometry: potential application to forensic science demonstrated by a modern horse-human study, J. Can. Soc. Forensic Sci, 39 (2) (2006) 47–54. [149] K. Alkass, B.A. Buchholz, H. Druid, K.L. Spalding, Analysis of 14 C and 13 C in teeth provides precise birth dating and clues to geographical origin, Forensic Sci. Int. 209 (1-3) (2011) 34–41. [150] A. Holobinko, W. Meier-Augenstein, H.F. Kemp, T. Prowse, S.M. Ford, 2 H stable isotope analysis of human tooth enamel: a new tool for forensic human provenancing? Rapid Commun. Mass Spectrom. 25 (7) (2011) 910–916. [151] J. Travis, Scientists decry ‘‘flawed’’ and ‘‘horrifying’’ nationality tests, http:// news.sciencemag.org/2009/09/scientists-decry-flawed-and-horrifyingnationality-tests, 2009 (accessed 4.03.15). [152] B.J. Smallwood, R.P. Philp, J.D. Allen, Stable carbon isotopic composition of gasolines determined by isotope ratio monitoring gas chromatography mass spectrometry, Org Geochem 33 (2002) 149–159. [153] G. O’Sullivan, R.M. Kalin, Investigation of the range of carbon and hydrogen isotopes within a global set of gasolines, Environ. Forensics 9 (2–3) (2008) 166– 176. [154] Y. Li, Y. Xiong, J. Fang, Q. Liang, J. Zhang, P. Peng, A new application of headspace single-drop microextraction technique for compound specific carbon isotopic determination of gasoline range hydrocarbons, Org. Geochem. 42 (2011) 559– 565. [155] S.-Y. Heo, W.J. Shin, S.-W. Lee, Y.-S. Bong, K.-S. Lee, Using stable isotope analysis to discriminate gasoline on the basis of its origin, Rapid Commun. Mass Spectrom. 26 (2012) 517–522. [156] S.D. Harvey, K.H. Jarman, J.J. Moran, C.M. Sorensen, B.W. Wright, Characterization of diesel fuel by chemical separation combined with capillary gas chromatography (GC) isotope ratio mass spectrometry (IRMS), Talanta 99 (2012) 262–269. [157] S. Muhammad, R.D. Frew, A.R. Hayman, Forensic differentiation of diesel fuels using hydrocarbon isotope fingerprints, Central Eur. Geol. 56 (1) (2013) 19–37. [158] S. Muhammad, A. Hayman, R Van Hale, R. Frew, Assessing carbon and hydrogen isotopic fractionation of diesel fuel n-alkanes during progressive evaporation, J. Forensic Sci. 60 (S1) (2015) S56–S65. [159] Z. Schwartz, Y. An, K. Konstantynova, G. Jackson, Analysis of household ignitable liquids and their post-combustion weathered residues using compound-specific gas chromatography-combustion-isotope ratio mass spectrometry, Forensic Sci. Int. 233 (1-3) (2013) 365–373. [160] D. Wakelin, Isotope ratio analysis of explosives – a new type of evidence, in: Proceedings of the 7th International Symposium on the Analysis and Detection of Explosives, Edinburgh, (2001), pp. 159–168. [161] C. Belanger, Application of EA-C-CF-IRMS in the analysis of explosives, in: Network Developing Forensic Applications of Stable Isotope Ratio Mass Spectrometry Conference, Kent, (2002), pp. 1–20. [162] M. J. Lott, J. Howa, J. R. Ehleringer, Locating the origins of explosives through stable isotope ratio analysis, http://www.forensic-isotopes.org/conference/ conf2002/conf2002.html, 2002, (accessed 19.06.11).

N. Gentile et al. / Forensic Science International 251 (2015) 139–158 [163] S.A. Phillips, S. Doyle, L. Philp, M. Coleman, Network developing forensic applications of stable isotope ratio mass spectrometry Conference 2002, Sci. Justice 43 (3) (2003) 153–160. [164] D. Wakelin, Origin identification of explosives by stable isotope analysis, 17th International Symposium on the Forensic Sciences, Forensic Science: Challenges & Changes, New Zealand, abstract, 2004. [165] A. Nissenbaum, The distribution of natural stable isotopes of carbon as a possible tool for the differentiation of samples of TNT, J. Forensic Sci. 20 (1975) 455–459. [166] R.B. Coffin, P.H. Miyares, C.A. Kelley, L.A. Cifuentes, C.M. Reynolds, Stable carbon and nitrogen isotope analysis of TNT: two-dimensional source identification, Environ. Toxicol. Chem. 20 (12) (2001) 2676–2680. [167] D. Widory, J.J. Minet, M. Barbe-Leborgne, Sourcing explosives: a multi-isotope approach, Sci. Justice 49 (2) (2009) 62–72. [168] C.M. Lock, Stable isotope profiling of energetic materials and their precursors, PhD Thesis, The Queen’s University of Belfast, Faculty of Engineering and Physical Sciences, 2009. [169] G. Pierrini, S. Doyle, C. Champod, F. Taroni, D. Wakelin, C. Lock, Evaluation of preliminary isotopic analysis (13 C and 15 N) of explosives. A likelihood ratio approach to assess the links between Semtex samples, Forensic Sci. Int. 167 (1) (2007) 43–48. [170] S.J. Benson, C.J. Lennard, P. Maynard, D.M. Hill, A.S. Andrew, C. Roux, Forensic analysis of explosives using isotope ratio mass spectrometry (IRMS) – preliminary study on TATP and PETN, Sci. Justice 49 (2) (2009) 81–86. [171] J.D. Howa, M.J. Lott, J.R. Ehleringer, Observations and sources of carbon and nitrogen isotope ratio variation of pentaerythritol tetranitrate (PETN), Forensic Sci. Int. 244 (2014) 152–157. [172] C.M. Lock, W. Meier-Augenstein, Investigation of isotopic linkage between precursor and product in the synthesis of a high explosive, Forensic Sci. Int. 179 (2-3) (2008) 157–162. [173] C.M. Lock, H. Brust, M.R. van Breukelen, J. Dalmolen, M. Koeberg, D.A. Stoker, Investigation of isotopic linkages between precursor materials and the improvised high explosive product hexamethylene triperoxide diamine, Anal. Chem. 84 (2012) 4984–4992. [174] J.D. Howa, M.J. Lott, L.A. Chesson, J.R. Ehleringer, Carbon and nitrogen isotope ratios of factory-produced RDX and HMX, Forensic Sci. Int. 240 (2014) 80–87. [175] J.J. Moran, C.J. Ehrhardt, J.H. Wahl, H.W. Kreuzer, K.L. Wahl, Integration of stable isotope and trace contaminant concentration for enhanced forensic acetone discrimination, Talanta 116 (2013) 866–869. [176] Royal Courts of Justice, R. v. Ibrahim, Omar, Osman and Mohamed, Case No 2007/ 04146/B5, approved judgement, 2008. [177] Court of Appeal – Criminal Division, R v Ibrahim & Ors, EWCA Crim 880, 2008. [178] J.E. Barnette, M.J. Lott, J.D. Howa, D.W. Podlesak, J.R. Ehleringer, Hydrogen and oxygen isotope values in hydrogen peroxide, Rapid Commun. Mass Spectrom. 25 (10) (2011) 1422–1428. [179] M. Ader, M.L. Coleman, S.P. Doyle, M. Stroud, D. Wakelin, Methods for the stable isotopic analysis of chlorine in chlorate and perchlorate compounds, Anal. Chem. 73 (20) (2001) 4946–4950. [180] N. Gentile, R.T. Siegwolf, O. Delemont, Study of isotopic variations in black powder: reflections on the use of stable isotopes in forensic science for source inference, Rapid Commun. Mass Spectrom. 23 (16) (2009) 2559–2567. [181] S.J. Benson, C.J. Lennard, P. Maynard, D.M. Hill, A.S. Andrew, C. Roux, Forensic analysis of explosives using isotope ratio mass spectrometry (IRMS)–discrimination of ammonium nitrate sources, Sci. Justice 49 (2) (2009) 73–80. [182] S.J. Benson, Introduction of isotope ratio mass spectrometry (IRMS) for the forensic analysis of explosives, PhD Thesis, University of Technology of Sydney, 2009. [183] S.J. Benson, C.J. Lennard, D.M. Hill, P. Maynard, C. Roux, Forensic analysis of explosives using isotope ratio mass spectrometry (IRMS) – Part 1: instrument validation of the DELTA XP IRMS for bulk nitrogen isotope ratio measurements, J. Forensic Sci. 55 (1) (2010) 193–204. [184] J.D. Howa, M.J. Lott, J.R. Ehleringer, Isolation and stable nitrogen isotope analysis of ammonium ions in ammonium nitrate prills using sodium tetraphenylborate, Rapid Commun. Mass Spectrom. 28 (2014) 1530–1534. [185] R. Aranda IV, L.A. Stern, M.E. Dietz, M.C. McCormick, J.A. Barrow, R.F. Mothershead II, Forensic utility of isotope ratio analysis of the explosive urea nitrate and its precursors, Forensic Sci. Int. 206 (1-3) (2011) 143–149. [186] J.R. Ehleringer, M.J. Lott, Stable isotopes of explosives provide useful forensic information, in: American Academy of Forensic Sciences Annual Meeting, San Antonio, (2007), p. p107. [187] R.R. McGuire, C.G. Lee, C.A. Velsko, E. Raber, Application of stable isotope ratios to the analysis of explosive residues, in: Proceedings of the 5th International Symposium on the Analysis and Detection of Explosives, Washington, DC, (1995), pp. 1–16. [188] V.F. Anisichkin, B.G. Derendyaev, V.A. Koptyug, I.Y. Malkov, N.F. Salakhutdinov, V.M. Titov, Investigation of the process of decomposition in a detonation wave by the isotope method, Fizika Goreniya i Vzryva 24 (3) (1988) 121–122. [189] A. Bernstein, Z. Ronen, E. Adar, R. Nativ, H. Lowag, W. Stichler, R.U. Meckenstock, Compound-specific isotope analysis of RDX and stable isotope fractionation during aerobic and anaerobic biodegradation, Environ. Sci. Technol. 42 (21) (2008) 7772–7777. [190] M. Berg, J. Bolotin, T.B. Hofstetter, Compound-specific nitrogen and carbon isotope analysis of nitroaromatic compounds in aqueous samples using solid-phase microextraction coupled to GC/IRMS, Anal. Chem. 79 (6) (2007) 2386–2393. [191] N. Gentile, L. Besson, D. Pazos, O. Dele´mont, P. Esseiva, On the use of IRMS in forensic science: proposals for a methodological approach, Forensic Sci. Int. 212 (2011) 260–271.

157

[192] L.J. Reidy, W. Meier-Augenstein, R.M. Kalin, 13 C-Isotope ratio mass spectrometry as a potential tool for the forensic analysis of white architectural paint: a preliminary study, Rapid Commun. Mass Spectrom. 19 (13) (2005) 1899– 1905. [193] N. Farmer, W. Meier-Augenstein, D. Lucy, Stable isotope analysis of white paints and likelihood ratios, Sci. Justice 49 (2) (2009) 114–119. [194] D.J. Croft, K. Pye, The potential use of continuous-flow isotope-ratio mass spectrometry as a tool in forensic soil analysis: a preliminary report, Rapid Commun. Mass Spectrom. 17 (23) (2003) 2581–2584. [195] D.J. Croft, K. Pye, Multi-technique comparison of source and primary transfer soil samples: an experimental investigation, Sci. Justice 44 (1) (2004) 21–28. [196] K. Pye, S.J. Blott, D.J. Croft, J.F. Carter, Forensic comparison of soil samples: assessment of small-scale spatial variability in elemental composition, carbon and nitrogen isotope ratios, colour, and particle size distribution, Forensic Sci Int 163 (1-2) (2006) 59–80. [197] N. Nic Daeid, W. Meier-Augenstein, H.F. Kemp, Investigating the provenance of un-dyed spun cotton fibre using multi-isotope profiles and chemometric analysis, Rapid Commun Mass Spectrom 25 (13) (2011) 1812–1816. [198] W. Meier-Augenstein, H.F. Kemp, E.R. Schenk, J. Almirall, Discrimination of unprocessed cotton on the basis of geographic origin using multi-element stable isotope signatures, Rapid Commun. Mass Spectrom. 28 (2014) 545–552. [199] R. Langel, J. Dyckmans, Combined 13 C and 15 N isotope analysis on small samples using a near-conventional elemental analyzer/isotope ratio mass spectrometer setup, Rapid Commun. Mass Spectrom. 28 (2014) 1019–1022. [200] N. Aziz, P.F. Greenwood, K. Grice, R. John Watling, W. van Bronswijk, Chemical fingerprinting of adhesive tapes by GCMS detection of petroleum hydrocarbon products, J. Forensic Sci. 53 (5) (2008) 1130–1137. [201] M.E. Dietz, L.A. Stern, A.H. Mehltretter, A. Parish, V. McLasky, R. Aranda IV, Forensic utility of carbon isotope ratio variations in PVC tape backings, Sci Justice 52 (1) (2012) 25–32. [202] M. Horacek, J.S. Min, S. Heo, J. Park, W. Papesch, The application of isotope ratio mass spectrometry for discrimination and comparison of adhesive tapes, Rapid Commun. Mass Spectrom. 22 (11) (2008) 1763–1766. [203] J.F. Carter, P.L. Grundy, J.C. Hill, N.C. Ronan, E.L. Titterton, R. Sleeman, Forensic isotope ratio mass spectrometry of packaging tapes, Analyst 129 (12) (2004) 1206–1210. [204] J.F. Carter, S. Doyle, B.-L. Phasumane, N. Nic Daeid, The role of isotope ratio mass spectrometry as a tool for the comparison of physical evidence, Sci. Justice 54 (5) (2014) 327–334. [205] E. Taylor, J.F. Carter, J.C. Hill, C. Morton, N. Nic Daeid, R. Sleeman, Stable isotope ratio mass spectrometry and physical comparison for the forensic examination of grip-seal plastic bags, Forensic Sci. Int. 177 (2-3) (2008) 214–220. [206] A.T. Quirk, J.M. Bellerby, J.F. Carter, F.A. Thomas, J.C. Hill, An initial evaluation of stable isotopic characterisation of post-blast plastic debris from improvised explosive devices, Sci. Justice 49 (2) (2009) 87–93. [207] N.L. Farmer, W. Meier-Augenstein, R.M. Kalin, Stable isotope analysis of safety matches using isotope ratio mass spectrometry-a forensic case study, Rapid Commun. Mass Spectrom. 19 (22) (2005) 3182–3186. [208] N.L. Farmer, A. Ruffell, W. Meier-Augenstein, J. Meneely, R.M. Kalin, Forensic analysis of wooden safety matches – a case study, Sci. Justice 47 (2) (2007) 88–98. [209] N. Farmer, J. Curran, D. Lucy, N. Nic Daeid, W. Meier-Augenstein, Stable isotope profiling of burnt wooden safety matches, Sci. Justice 49 (2) (2009) 107–113. [210] The United States Department of Justice, Amerithrax investigative summary. Released pursuant to the freedom of information act, http://www.justice.gov/ amerithrax/docs/amx-investigative-summary.pdf, 2010, (accessed 18.08.13). [211] J.R. Ehleringer, S.M. Matheson, Stable isotopes and courts, Utah Law Rev. 2 (2010) 385–442. [212] J. Horita, A.A. Vass, Stable-isotope fingerprints of biological agents as forensic tools, J. Forensic Sci. 48 (1) (2003) 122–126. [213] H.W. Kreuzer-Martin, M.J. Lott, J. Dorigan, J.R. Ehleringer, Microbe forensics: oxygen and hydrogen stable isotope ratios in Bacillus subtilis cells and spores, Proc. Natl. Acad. Sci. U.S.A. 100 (3) (2003) 815–819. [214] H.W. Kreuzer-Martin, L.A. Chesson, M.J. Lott, J.V. Dorigan, J.R. Ehleringer, Stable isotope ratios as a tool in microbial forensics-Part 1. Microbial isotopic composition as a function of growth medium, J. Forensic Sci. 49 (5) (2004) 954–960. [215] H.W. Kreuzer-Martin, L.A. Chesson, M.J. Lott, J.V. Dorigan, J.R. Ehleringer, Stable isotope ratios as a tool in microbial forensics – Part 2. Isotopic variation among different growth media as a tool for sourcing origins of bacterial cells or spores, J. Forensic Sci. 49 (5) (2004) 961–967. [216] H.W. Kreuzer-Martin, L.A. Chesson, M.J. Lott, J.R. Ehleringer, Stable isotope ratios as a tool in microbial forensics-part 3. Effect of culturing on agar-containing growth media, J. Forensic Sci. 50 (6) (2005) 1372–1379. [217] H.W. Kreuzer-Martin, K.H. Jarman, Stable isotope ratios and forensic analysis of microorganisms, Appl. Environ. Microb. 12 (2007) 3896–3908. [218] A. van Es, J. Koeijer, G. van der Peijl, Discrimination of document paper by XRF, LA-ICP-MS and IRMS using multivariate statistical techniques, Sci. Justice 49 (2) (2009) 120–126. [219] K. Jones, S. Benson, C. Roux, The forensic analysis of office paper using carbon isotope ratio mass spectrometry-part 1: understanding the background population and homogeneity of paper for the comparison and discrimination of samples, Forensic Sci. Int. 231 (1-3) (2013) 354–363. [220] K. Jones, S. Benson, C. Roux, The forensic analysis of office paper using carbon isotope ratio mass spectrometry-part 2: method development, validation and sample handling, Forensic Sci. Int. 231 (1-3) (2013) 364–374.

158

N. Gentile et al. / Forensic Science International 251 (2015) 139–158

[221] K. Jones, S. Benson, C. Roux, The forensic analysis of office paper using carbon isotope ratio mass spectrometry. Part 3: Characterizing the source materials and the effect of production and usage on the d13 C values of paper, Forensic Sci. Int. 233 (1-3) (2013) 355–364. [222] I. Tea, I. Antheaume, B.-L. Zhang, A test to identify cyanide origin by isotope ratio mass spectrometry for forensic investigation, Forensic Sci. Int. 217 (1-3) (2012) 168–173. [223] H.W. Kreuzer, J. Horita, J.J. Moran, B.A. Tomkins, D.B. Janszen, A. Carman, Stable carbon and nitrogen istope ratios of sodium and potassium cyanide as a forensic signature, J. Forensic Sci. 57 (1) (2012) 75–79. [224] H.W. Kreuzer, J.B. West, J.R. Ehleringer, Forensic applications of light-element stable isotope ratios of ricinus communis seeds and ricin preparations, J. Forensic Sci. 58 (S1) (2013) S43–S51.

[225] G. Van der Peijl, S. Montero, W. Wiarda, P. de Joode, Isotopic and other investigations in relation to a safe burglary, in: Proceedings of the 17th International Symposium on the Forensic Sciences Handbook and Progra, 2004. [226] F. Roelofse, U.E. Horstmann, A case study on the application of isotope ratio mass spectrometry (IRMS) in determining the provenance of a rock used in an alleged nickel switching incident, Forensic Sci. Int. 174 (1) (2008) 64–67. [227] G. Michalski, S. Earman, C. Dahman, R.L. Hershey, T. Mihevc, Multiple isotope forensics of nitrate in a wild horse poisoning incident, Forensic Sci. Int. 198 (1-3) (2010) 103–109. [228] J.J. Moran, H.W. Kreuzer, A. Carman, J.H. Wahl, D.C. Duckworth, Multiple stable isotope characterization as a forensic tool to distinguish acid scavenger samples, J. Forensic Sci. 75 (1) (2012) 60–63.