Headspace mode of liquid phase microextraction: A review

Accepted Manuscript Headspace mode of liquid phase microextraction: A review Mohammad Reza Afshar Mogaddam, Ali Mohebbi, Azar Pazhohan, Fariba Khodadadeian, Mir Ali Farajzadeh PII:

S0165-9936(18)30438-2

DOI:

https://doi.org/10.1016/j.trac.2018.10.021

Reference:

TRAC 15285

To appear in:

Trends in Analytical Chemistry

Received Date: 27 August 2018 Revised Date:

17 October 2018

Accepted Date: 22 October 2018

Please cite this article as: M.R. Afshar Mogaddam, A. Mohebbi, A. Pazhohan, F. Khodadadeian, M.A. Farajzadeh, Headspace mode of liquid phase microextraction: A review, Trends in Analytical Chemistry, https://doi.org/10.1016/j.trac.2018.10.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Headspace mode of liquid phase microextraction: A review

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Mohammad Reza Afshar Mogaddam1,2 ,Ali Mohebbi3, Azar Pazhohan4, Fariba Khodadadeian2, Mir

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Ali Farajzadeh3,5*

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4 Food and Drug Safety Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

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Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

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Department of Analytical Chemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran

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Academic Center for Education, Culture and Research, East Azarbaijan, Tabriz, Iran

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Engineering Faculty, Near East University, 99138 Nicosia, North Cyprus, Mersin 10, Turkey

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Tel.: +98 41 33393084

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*Corresponding author: M.A. Farajzadeh

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E–mail address: [email protected]; [email protected]

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Fax: +98 41 33340191

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In recent years, liquid phase microextraction (LPME) as a solvent–minimized and microscale

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implementation of sample pretreatment procedure of liquid–liquid extraction has been introduced and

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obtained great attention among the researchers due to its simplicity, low cost, rapidity, and efficiency.

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Developments have led to different approaches of LPME such as headspace mode of liquid phase

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Abstract

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In HS mode of LPME, the extractant is suspended in the headspace of analytes solution and has no

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contact with the sample solution which leads to eliminate interferences problem. The present review

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discusses HS mode of LPME with the focus on its historical developments, principles, configurations,

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inherent limitations, and pros and cons. Herein, recent analytical applications of the method used in

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the isolation and trace enrichment prior to analysis of various compounds are reviewed. The future

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direction of the researches in this field and general trend toward the commercial applications are also

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considered.

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microextraction (HS mode of LPME) which is used in the cases of volatile and semi–volatile analytes.

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Single drop microextraction; Single drop microextraction

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Keywords: Headspace mode of liquid phase microextraction; Sample preparation; Miniaturization;

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In recent years, the development of sensitive, fast, and accurate analytical methods has become a vital

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issue in analytical chemistry. Despite the great instrumental advances, most of these equipment cannot

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handle sample matrices directly and an additional step called sample preparation is needed. The basic

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concept of this step is to enhance the concentration of target analytes (enrichment), reduce the

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presence of matrix components (sample clean–up), and convert a sample into a format compatible

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with analysis system, which indicates its importance in analyzing and determining the target analytes

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1. Introduction

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(LLE) and solid–phase extraction (SPE) have been widely used for this purpose. LLE suffers from

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especially in the cases of complex matrices. Classical treatments such as liquid–liquid extraction

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automation and on–line connection to the analysis system. SPE is also time consuming and using

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expensive and commercially limited cartridges which limited its use [1, 2]. Driven by the need to

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circumvent these problems and cease the quest for novel sample pretreatment methods,

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microextraction methods including solid phase microextraction (SPME), and liquid phase

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microextraction (LPME) were developed. The general idea behind these methods is the elimination of

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organic solvent consumption or great reduction in the ratio of the extraction solvent to sample

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volume. SPME is a solvent–free process introduced in 1990 by Pawliszyn and is based on the

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some drawbacks such as high consumption of organic solvents, emulsion formation, difficulty in

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[3]. This method is regarded as an accurate and sensitive sample pretreatment. Despite these

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advantages, SPME is still relatively expensive, suffers from sample carry over problem, and the used

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commercial fibers are fragile. LPME, a solvent–minimized and microscale implementation of sample

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pretreatment procedure of LLE, can overcome these problems. It demands a little organic solvent,

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requires inexpensive and simple device, and provides high enrichment factors. The principle of LPME

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is based on the partitioning of analytes between sample matrix (donor phase) and an extraction solvent

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(acceptor phase) [1]. Generally, there are two modes of LPME depending on the types of analytes

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being extracted and the complexity of the matrix: direct LPME and headspace mode of liquid phase

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partitioning of analytes between sample solution and a fused silica fiber coated with a stationary phase

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Cantwell in which a single extracting solvent drop (8 µL of solvent) suspended on a Teflon rod

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exposed with the stirred sample solution containing the analytes [4]. The analytes were enriched into

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the organic solvent microdrop. This method is fast, simple, inexpensive, requires a little organic

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solvent and produces a little waste. Disadvantage of this method, is that the extraction and injection

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microextraction (HS mode of LPME). The first mode of LPME was introduced by Jeannot and

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was performed using a conventional microsyringe as the organic solvent holder by He and Lee [5]. In

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this method, firstly 1 µL of an organic solvent was withdrawn into the microsyringe, and afterward

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the microsyringe needle immersed in the liquid sample by passing through the sample vial septum. A

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droplet of the solvent was suspended at the tip of the syringe needle in the stirred aqueous sample

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containing the analytes. After performing the extraction procedure, the organic phase was withdrawn

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back into the microsyringe and injected to the analytical instrument for quantification of the analytes.

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The mentioned method is mostly recommended for the relatively clean samples (e.g. tap water or

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groundwater) and the extraction of non–volatile compounds. In 2001, Theis et al. [6] introduced HS

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mode of LPME as another version of LPME that simultaneously takes advantages of LPME and

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have to be performed separately with different apparatus. To solve this problem, one year later, LPME

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sample containing the analytes and thermostated at a given temperature for a pre–set extraction time.

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The volatile and semi–volatile analytes are enriched into the organic solvent microdrop.

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conventional headspace sampling. In this method the extracting phase is placed above the stirred

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and cons, and applications of HS mode of LPME as an efficient and widely used sample pretreatment

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The aim of the present review was to discuss principles, configurations, limitations, automation, pros

method especially for analytes with relatively high vapor pressure. Finally, we look ahead to future

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potential developments of this method.

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2. Principles of HS mode of LPME

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As its name implies, HS mode of LPME is a combination of headspace sampling and LPME in which

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an acceptor (organic solvent) or extracting phase is placed above the stirred sample containing the

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analytes at a given temperature. This method is recommended for the extraction of the volatile and

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semi–volatile compounds. In HS mode of LPME, the extraction system consists of a microsyringe, a

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mode of LPME, the vial containing the analytes is placed on a magnetic stirrer, then the needle tip of

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microsyringe containing the organic solvent passed through the septum of the vial and fixed about

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0.5–1.0 cm above the sample solution. Afterward, the sample solution is continuously agitated.

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Actually, in this method, the analytes are distributed among three phases including the sample,

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vial containing the sample, a cap to avoid loss of the analytes and solvent, and a stirrer bar. In HS

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injected into the analysis system for the quantitative analysis. The rate–determining step of the HS

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mode of LPME is the transfer of the analytes from the sample to the headspace because diffusion rate

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in the headspace is faster than that in the sample. Therefore, a high stirring speed is needed to improve

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mass transfer among the phases by increasing the contact area of the analytes and extractant. In HS

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mode of LPME, the parameters related to the donor and acceptor phases such as type and volume of

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extraction solvent, sample volume, ionic strength, extraction time, stirring rate, temperature, and pH

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of sample solution should be investigated and optimized. Among these factors, selection of extraction

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solvent type is the most important one and there are some requirements and limitations in choosing an

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appropriate solvent for HS mode of LPME. First of all, the selected solvent should possess a low

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headspace, and organic solvent. Finally, the microsyringe needle is removed from the vial and

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peak produced by the extractant should not interfere with the chromatographic peaks of the selected

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analytes. Unlike immersion mode of LPME in which water–immiscible solvents are used, in the HS

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vapor pressure so that it does not evaporate during the extraction procedure. Furthermore, the solvent

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extraction of analytes from an aqueous phase. But, in the case of the most of water–miscible solvents,

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mode of LPME both of the water–immiscible and water–miscible solvents can be used for the

the drop size may increase during the extraction process causing the drop to fall from the needle. To

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meet these requirements, in addition to the conventional organic solvents such as n–octanol, ionic

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liquids (ILs) were also employed as the extraction solvent in HS mode of LPME, since they possess

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high thermal stability and negligible vapor pressure. The other important factor is the temperature of

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sample which can affect kinetics and thermodynamics of the HS mode of LPME process by varying

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the Henry's constants and diffusion coefficients of analytes which lead to change the vapor pressure

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and the concentration of the analytes in the headspace. Although other factors are not as important as

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the type of extraction solvent and temperature of sample but they also need precise optimization.

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such as central composite design, Box–Behnken design or others to reach high enrichment factors

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and extraction recoveries (ERs).

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3. Configurations of HS mode of LPME

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different modes named as headspace single drop microextraction (HS–SDME), and hollow fiber (HF)

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supported HS mode of LPME which will be discussed in the following sections. Different

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configurations of these modes are schematically shown in Figure 1.

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HS mode of LPME attracted great attention since its introduction in 2001 and mainly classified in two

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3.1. HS–SDME

Fig. 1

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microdrop HS mode of LPME or static HS–SDME, a microdrop of an organic solvent is suspended

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from the needle tip of a gas chromatography (GC) microsyringe and the needle placed in the

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headspace above a stirred sample thermostated at a given temperature for a pre–set extraction time

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In the first and simplest version of HS mode of LPME developed by Theis et al. and known as

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then is retracted back into the microsyringe and injected into GC for the identification and

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quantification of the extracted analytes. Like all of the HS–based methods, the acceptor phase does

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[6]. The drop remains at the tip of the microsyringe throughout the period of extraction procedure and

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no interference problem which makes analyte identification and quantification more reliable. In

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not contact with the sample, and components of the sample matrix are mostly eliminated, so there is

addition, since solvent and a microsyringe only are involved, this method has the advantages of low

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cost, ease of operation, and no carryover problem. Also, in comparison to the direct immersion mode,

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the selection of extractant is flexible and there is no need to consider the solvent solubility in the

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sample solution. Despite these advantages, like other sample pretreatment methods there are some

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problems associated with this method. For instance, the surface area of the used organic solvent is

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limited, therefore, low interfacial contact area between sample and extraction solvent may decrease

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the extraction efficiency. In addition, the volume of the suspended organic solvent is limited because

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there is no support for it, except microsyringe needle. Therefore, the organic solvent would detach

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solve this problem, Shen and Lee in 2003, introduced a dynamic mode of HS–SDME in which an

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organic solvent film is formed within a microsyringe barrel and used as the extraction interface [7]. In

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this method, the spherical drop is transformed in a film and the extraction procedure takes place

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within the microsyringe barrel. The extraction procedure comprised of drawing 2 µL of organic

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from the tip of the needle, so careful and elaborate manual operation is required in the experiment. To

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passed through the vial septum and placed above the sample. Then, 5 µL of the gaseous sample was

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withdrawn into microsyringe and maintained for a period of time, and then the plunger was depressed

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back to the original mark. The same sampling process was repeated for 25 times. At the end, the

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microsyringe needle was removed and injected into the GC for quantitative analysis. Compared to the

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previous mode, the described method provided higher extraction efficiency within a short analysis

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time [5, 7]. This attributed to very small space within the microsyringe barrel which led to the fast

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equilibrium between gaseous analytes and the organic solvent film. Even though, there is no

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individual review with the subject of HS–SDME but its different aspects were discussed in the

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previously published reviews with the titles of SDME or LPME. For example, the principle and

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solvent (cyclohexane) into a commercial GC microsyringe, afterward the microsyringe needle was

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number of reviews were focused on the combination of SDME and its derivates like HS–

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SDME with various analytical techniques such as ultraviolet–visible spectrophotometry [11]

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developments of HS–SDME were discussed in the published reviews [1, 8–10]. In addition, a

and chromatography [12].

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3.2. HF supported HS mode of LPME

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Another method termed as HF supported HS mode of LPME, in which the extractant droplet was held

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above the sample with the aid of HF was introduced by Lee and co–workers in 2005 [13]. In this

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method µL–level of an acceptor or extraction solvent was withdrawn into a microsyringe with the

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conic needle tip. The sample vial septum was pierced by the microsyringe. Afterward, the needle tip

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was inserted into a HF and then the fiber was immersed in the extractant for a few seconds in order to

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impregnation of the porous wall. Then, the vial was placed in the position and capped so that the fiber

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programmable syringe pump was used for moving the solvent within the fiber. The movement

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facilitated mass transfer from the sample to the solvent. This method enabled the use of high solvent

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volumes and the surface area of the extraction phase in contact with the headspace was increased

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dramatically. In addition, because of low cost and simplicity of extraction device the HF can be

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together with the needle of microsyringe assembly was placed in the headspace region. In this study, a

changed after each experiment to avoid cross–contamination and carryover between extractions which

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leads to high repeatability.

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4. Applications of HS mode of LPME 4.1. HS–SDME

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for the extraction of compounds with relatively high vapor pressure. In the first report of HS–SDME,

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benzene, toluene, ethyl benzene and xylene (BTEX) were extracted into the suspended n–octanol drop

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[6]. In this method a single drop was hanged from the tip of a syringe and after extraction, the drop

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was sucked into the syringe and used for analysis. This method was the classical form of HS–SDME

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After introducing SDME methods, its performance in HS–SDME mode has attracted more attentions

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[16], ammonia [17], amphetamine and methamphetamine [18], BTEX [19], butyltin compounds [20],

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chloride [21], cyanide [22], chlorobenzene [23], fluoride [24], methylcyclopentadienyl–manganese

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and it was used for the extraction of many compounds including acetone [14], n–alkanes [15], amitraz

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mononitrotoluenes [30], organophosphorus pesticides [31], polycyclic aromatic hydrocarbons (PAHs)

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tricarbonyl [25], valporic acid [26], phenolic compounds [27], bromide [28], methylmercury [29],

[32, 33], selenium [34], and short chain fatty acids [35]. In these methods, the extracted analytes into

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drop were analyzed by separation methods such as GC, high performance liquid chromatography or

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capillary electrophoresis and spectrometry methods such as atomic absorption spectrometry, or

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ultraviolet spectrophotometry). Designing electrochemical sensors for the analysis of the selected

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analytes after HS–SDME was considered as another instrumental analysis. In some procedures,

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derivatization step was done before the analysis to enhance the analytes volatility or detectability. In

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different papers, derivatization process was occurred simultaneously or asynchronous with HS–

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SDME. Determination of acetone [36], aliphatic amines [37], carbonyl compounds [38], amphetamine

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performed using simultaneous derivatization and HS–SDME. For this purpose, the derivatization

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reagents were mixed with the used extraction solvent and the mixture was placed at the tip of a

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syringe to contact with the analytes in the headspace of solution. The analytes were derivatized in

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drop along with dissolving into it [42]. In all of these methods, the effective parameters were

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and methylenedioxyamphetamine [39], volatile organic acids [40], and hexanal and heptanal [41] was

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on the employing high–viscosity extraction solvents with low volatility like ILs to overcome some

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disadvantages of the classical HS–SDME such as drop instability, limited drop size, and evaporation

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of the drop. In the first report in 2003, a few microliters of 1–octyl–3–methylimidazolium

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hexafluorophosphate was suspended from tip of a syringe and PAHs were extracted into the used ILs

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[43]. The efficiency of this method was compared with the classical HS–SDME performed with n–

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octanol and the results showed that longer extraction time and much larger drop volume were

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accessible in IL–based HS–SDME. This procedure was developed for the determination of

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chlorinated anilines from environmental water samples [44]. In this method extraction was performed

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in an elevated temperature in order to transfer the analytes to the headspace of solution,. Recently, a

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optimized using “one–variable–at–a–time” strategy. In recent advances, a number of papers focused

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[45] and chlorobenzenes [46] followed by GC determination. In these methods the magnetic ILs were

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held at the bottom of a rod–shaped magnet and it was fixed in the headspace of sample solution. After

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magnetic rod along with magnetic ILs were used instead of syringe for the determination of alkanes

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analytes were desorbed from ILs by thermal desorption. This method showed high sensitivity and

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extraction of the analytes into the ILs, the magnetic rod was placed in mobile phase track and the

simplicity and considered as a green method owing to use ILs. Analytical features of the developed

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HS–SDME methods are shown in Table 1. A number of reviews were focused on the applications of

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SDME and its various types in different fields [47], and on specific areas including the determination

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of pesticide residues [48].

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4.2. Microwave/ultrasonic–assisted HS mode of LPME

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Transferring analytes to the headspace of sample solution is an important parameter in the success of

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an HS mode of LPME method. Usually stirring of the sample solution is performed for this purpose.

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extraction of chlorobenzenes from water samples. In this paper the HS–SDME procedure was

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performed in a microwave oven and the analytes transferring into the extraction solvent was strongly

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increased. In this method high ERs were obtained compared to the case that the microwave

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irradiations were not used. In other work instead of microwave irradiations, the efficiency of HS mode

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In 2007, Canals and co–workers [49] developed microwave–assisted–HS–SDME procedure for

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preconcentrate chlorophenols from aqueous samples [50]. In this method, a cone–shaped tube was

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used to hold the extraction solvent droplet and more solvent could be suspended in the tube than

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microsyringe due to the larger interfacial tension. The results showed that the analysis sensitivity was

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significantly improved with the increasing the extractant volume. In another published paper,

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sonication was used in the formation of aerosols of sample solution and their transferring into the

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extraction solvent [51]. In fact, in this method the sample solution was nebulized into the headspace

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of the solution and the aerosols of the sample solution was transferred into the solvent. Some

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characteristics of the methods are listed in Table 2.

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of LPME procedure was enhanced with the aid of sonication and the developed method was used to

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HF supported HS mode of LPME is another form of HS based methods in which the extraction

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solvent is placed in the pores of an HF. In this method some disadvantages of HS–SDME like drop

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4.3. HF supported HS mode of LPME

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method was developed for the extraction and preconcentration of PAHs from soil samples [13]. In this

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instability and solvent loss are removed. In 2005, for the first time, HF–based HS mode of LPME

paper n–octanol was placed in the pores of an HF and inserted in the headspace of soil sample. The

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volatile PAHs were extracted into the n–octanol and then the extractant was injected into the analysis

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system. In this method large volume of extraction solvent could be used instead of drop–based HS–

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SDME method. Up to know, this method was developed for the extraction of organochlorine

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pesticides [52], residual monomers in latex [53], and volatile organic compounds [54]. In 2009, HF–

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based HS mode of LPME along with derivatization was used for the determination of free cyanide in

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biological samples [55]. In this work, the derivatization reagent and extraction solvent were placed in

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the pores of the HF and the analyte was derivatized in the HF.

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In the past years, in order to stabilize the suspended drop and enabling the application of larger drop

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volume in HS–SDME, various modifications of the syringe–needle tip such as bell–mouthed device

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[56], flange rod [57], stainless steel net [58] and brass funnel [59] have been used. In 2016, Zaruba et

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4.4. New configuration in HS mode of LPME method

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spectrophotometer for determination of sulfite in the food samples [60]. This approach avoids the

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necessity of handling the drop between the extraction and detection steps and enables the online

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monitoring of the entire extraction process which makes the analysis simpler and less time–

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consuming. In 2016, Farajzadeh et al. [61] developed a new home–made extraction device for

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al. used an optical probe as a microdrop holder in HS–SDME procedure in combination with a

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containing µL–level of an extraction solvent was inserted in the headspace of sample solution. This

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method is dynamic form of HS mode of LPME due to continuously passing of the analytes through

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the extraction vessel. The developed method was successfully used for the determination of 1,4–

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dioxane in shampoo [62], pyridine as a decomposition product in ceftazidime and mouthwash solution

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performing HS mode of LPME method. In this method, a GC liner shaped extraction vessel

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performed using a paper–based analytical device for the extraction of hydrogen sulfide from fuel oils

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[65]. In this method instead of a microsyringe, a deflagrating spoon was used to hold the extraction

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solvent drop.

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[63], and residual solvents in pharmaceuticals [64]. Recently a new HS mode of LPME method was

5. Automation of HS mode of LPME

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A significant useful aspect of implementing the microextraction methods in analytical laboratories is

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the automation of these techniques which can lead to improve via ease of the operation and to achieve

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high repeatability in sample extraction. Also, a large number of samples can be analyzed by the

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automated techniques. So, with the advent of microextraction methods, attempts were made to

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automate them and the first automated drop–based system was developed in 1995 [66]. After that,

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several automated systems involving extraction of target analytes into an immersed single drop or

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automated system was published in 2006 for the extraction and preconcentration of BTEX from

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aqueous samples [69]. For this purpose, the plunger of a syringe was connected to a rotating disk

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motor and the syringe containing a thin film of an organic solvent was contacted with the headspace

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of sample solution. The analytes in headspace of the solution was extracted into the thin film while

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liquid film were developed [67, 68] in the case of HS mode of LPME. The first report of fully

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operation considerably improved the surface area of the boundary using a very small amount of an

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extraction solvent, thereby the extraction efficiency was increased. The use of a commercial

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autosampler for the HS mode of LPME was considered in the other work in the determination of ten

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musk fragrance from environmental samples [70]. In this method, a few microliters of 1–octyl–3–

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methylimidazolium hexafluorophosphate was suspended from tip of an autosampler plunger and after

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extraction it was injected into separation system. Good repeatability and extraction efficiency were

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obtained, comparable with manual HS mode of LPME with apparent saving in human effort. In other

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work, the efficiency of the mentioned method was compared with automated–SPME for extraction of

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the residual solvents from edible oil samples and the results showed that high sensitivity and good

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this film reformed on the inner surface of the syringe each time the plunger was pulled back. This

repeatability were obtainable [71].

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6. Future remarks

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compounds has attracted great attention since its invention. Some disadvantages of this method can be

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HS mode of LPME as an efficient technique for the extraction of volatile and semi–volatile

removed by designing special instruments to hold extraction solvent drop. The use of deep eutectic

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solvents as green and novel solvents is anticipated due to their similar properties with ILs. On the

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other hand, combination of other microextraction techniques with HS mode of LPME is still very

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limited and it is expected that many studies will be taken up in this field.

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7. Conclusions

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In this work development of different HS mode of LPME methods including HS–SDME and HF–HS

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mode of LPME and their applications for the extraction and preconcentration of different compounds

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methods as environmentally friendly procedures. These methods were automated by different sets up

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and therefore their use in routine analytical experiments is possible. On the other hand, extraction of

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different analytes from solid samples can be performed easily. These methods are still admired and

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their new improvements are in progress.

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in the various samples were reviewed. The use of ILs as the extraction solvent classifies these

Acknowledgements

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References:

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The authors thank the Research Council of Tabriz University for the financial support.

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516

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microextraction coupled to GC–MS/MS to determine musk fragrances in environmental water

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Figure caption:

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522 523 524 525 526 527 528 529 530

HF supported HS mode of LPME.

531

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Fig. 1. Configurations of HS mode of LPME: (A) static HS–SDME, (B) dynamic HS–SDME, and (C)

20

532 533 534

ACCEPTED MANUSCRIPT Table 1. Applications of HS–SDME method for the determination of different compounds. Analytical technique

LOD a)

EF b)

RSD% c)

References

Ethanol in water (40%, w/v)

Fluorospectrometer

–

5.0

[9]

Water samples

n–Dodecane

GC–FID d)

55–809

2.3–7.2

[10]

Amitraz

Honey

n–Dodecane

GC–TSD e)

–

4.8–7.7

[11]

Ammonia

Human blood, seawater and milk

Phosphoric acid (0.5 mM)

CE f)

14

5.3

[12]

Amphetamine and methamphetamine

Urine samples

Octane

500–730

5–7

[13]

BTEX

Water samples

n–Hexadecane

–

6.9–9.6

[14]

Butyltin compounds

–

1.1–10.1

[15]

Chloride

Environmental and biological samples Water and salts

–

5.6

[16]

Cyanide

Water sample

Ninhydrin dissolved in carbonate buffer

Microspectrophotometry

–

3.9

[17]

Chlorobenzenes

Water samples

n–Hexane

GC–ECD j)

–

<6

[18]

Fluoride

Milk

Sodium carbonate (9 mM)

Ion chromatography

97

0.24–1.0

[19]

Methylcyclopentadienyl–manganese tricarbonyl Valporic acid

Water samples

Octane

GC–MS k)

2100

6.4

[20]

n–Dodecane

GC–FID

0.26 (µg g–1) 0.1–4.0 (ng mL–1) 10 (ng g–1) 25.5 (ng mL–1) 0.5 (ng mL–1) 0.72–5.0 (ng mL–1) 8×10 -4–0.0014 (ng mL–1) 2.8 (ng mL–1) 4.3 (ng mL–1) 0.004–0.008 (ng mL–1) 3.8 (ng mL–1) 0.21 (ng mL–1) 800 (ng mL–1) 0.35–5.8 (ng mL–1) 1.3 (ng mL–1)

27

<13.2

[21]

–

0.7–7.4

[22]

243

4.4

[23]

40

7.0

[24]

103–142

–

[25]

23–109

1.7–10

[26]

9–159

–

[27]

n–Alkanes

Bromide

Water samples

Methyl mercury

Water sample

Mononitrotoluenes

Wastewater

Organophosphorus pesticides

Water and fruit juices samples

PAHs

Water samples

PAHs

Environmental samples

Se

Water samples

Short–chain fatty acids

Asphaltenes

Water

GC–FID

GC–ICP–MS h) UV–Vis i)

n–Dodecane

HPLC–UV

20 µM fluorescein aqueous solution containing dimethyl formamide 2% (v/v) HCl solution (1 M)

Fluorospectrometer

n–Amyl alcohol

GC–FID

Toluene

GC–FPD m)

1–Butanol

GC–FID

Aqueous solution of β–cyclodextrin

HPLC–UV

1.5–28 (ng mL–1)

18–53

5.6–7.1

[28]

30 mg L–1 of Pd (NO3)2 in 1.5% (w/v) HNO3 1–Butanol

ET–AAS

0.15 (ng mL–1) 0.02–0.3 (ng mL–1)

25

3.0

[29]

–

3.7–5.0

[30]

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Phenolic compounds

Human serum and pharmaceutical preparations Biomass smoke

Decane

HPLC–UV g)

SC

Cosmetic samples

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Sample

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Extraction solvent

Analytes

ET–AAS l)

GC–FID

4.0 (ng mL–1) 0.02–0.06 (ng mL–1) 0.21–0.56 (ng mL–1) 4–41 (ng mL–1)

ACCEPTED MANUSCRIPT

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a) Limit of detection b) Enrichment factor c) Relative standard deviation d) Gas chromatography–flame ionization detector e) Gas chromatography–thermionic specific detector f) Capillary electrophoresis g) High performance liquid chromatography–ultraviolet detector h) Gas chromatography–inductively coupled plasma–mass spectrometry i) Ultraviolet–visible spectrometry j) Gas chromatography–electron capture detector k) Gas chromatography–mass spectrometry l) Electrothermal–atomic absorption spectrometry m) Gas chromatography–flame photometric detector

MANUSCRIPT Table 2. Applications of microwave/ultrasonic–assisted HS mode of LPME for ACCEPTED the determination of different compounds. Analytical technique

LOD a)

RSD% b)

RR% c)

References

Water samples

[C6MIM] [PF6]

HPLC–PDA d)

0.016–0.039 (ng mL–1)

2.3–8.3

81.7–105.5

[49]

Chlorophenols

Water samples

Acetonitrile 50% (v/v)

HPLC–UV e)

6–23 (ng mL–1)

2.4–9.1

84.6–100.7

[50]

Essential oil

Cuminum cyminum L.

6.67–14.8 (pL L–1)

–

–

[51]

Sample

Chlorobenzenes

n–Heptadecane

GC–MS f)

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a) Limit of detection b) Relative standard deviation c) Relative recovery d) High performance liquid chromatography– photodiode array e) High performance liquid chromatography– ultraviolet detector f) Gas chromatography–mass spectrometry

RI PT

Extraction solvent

Analytes

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ACCEPTED MANUSCRIPT Highlights ► Historical developments and principles of HS mode of LPME have been reviewed. ►Pros and cons of HS mode have been discussed.

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► Future potential developments have been prospected.

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► Analytical applications and automation have been covered.