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Chemical characterization of counterfeit captagon tablets seized in Jordan
Forensic Science International 152 (2005) 185–188 www.elsevier.com/locate/forsciint
Chemical characterization of counterfeit captagon tablets seized in Jordan Mahmoud A. Alabdalla* Forensic Science Laboratory, Department of Chemical Analysis, P.O. Box: 330069, Amman 11134, Jordan Received 6 January 2004; received in revised form 6 August 2004; accepted 10 August 2004 Available online 1 October 2004
Abstract Fenethylline, commonly known by the trademark name ‘captagon’, is one of the most popular drugs of abuse among the young affluent communities of the Middle East. The Drug Control Department of the Public Security Directorate of Jordan has put captagon under control in the year 1988. Samples from 124 batches seized were analyzed by means of gas chromatograph– mass spectrometry (GC–MS). The analysis demonstrates the presence of amphetamine, caffeine and several other substances, besides, the absence of fenethylline. Based on GC–MS analytical data, comparisons were made between the various samples to determine the similarities and obtain inferences with respect to commonality of origin. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Counterfeit; Captagon; GC–MS; Tablets
1. Introduction Fenethylline, [7-(2-a-methylphenyl-aminoethyl)-theophylline], a synthetic-type stimulant, has become one of the most widely used illicit substances in the Middle East [1]. In the 1980s, the legal production of captagon tablets was ceased and the illicit production of the drug has increased [2]. Jordan is geographically located between drug producing countries to the north and drug consuming countries to the south and west. This has made, and continues to make Jordan a transient country for counterfeit captagon tablets. Although captagon is no longer in clinical use in Jordan since it’s banning in 1988, the country has witnessed a rise in the number of drug abusers. Investigators working on the characterization of counterfeit captagon tablets have directed their work to the use of ultraviolet (UV), infrared (IR) spectroscopic methods and thin layer chromatography (TLC) for the purpose of determining major active ingre* Tel.: +962 77 728758; fax: +962 6 5515119. E-mail address: [email protected].
dients present in these tablets [3,4]. GC–MS was chosen to identify as many potential substances as possible in counterfeit captagon tablets from different drug seizers. The chemical composition of each tablet was determined, and their chromatographic patterns were compared for the purpose of establishing links between different seizures.
2. Experimental 2.1. Materials and reagents One hundred and twenty-four batches of illicit captagon tablets seized by the Drug Control Authorities were received at different intervals. Each batch contained 5–15 tablets. Their chemical composition was compared with that of the legal standards available in the author’s laboratory. All reagents used where of analytical or HPLC grade. Solidphase extraction columns (ISOLUTE1) were supplied from International Sorbent Technology Ltd. Mid Glamorgan U.K.
0379-0738/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.forsciint.2004.08.004
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M.A. Alabdalla / Forensic Science International 152 (2005) 185–188
2.2. Gas chromatography
Table 1 Retention times of substances detected
GC–MS was carried out on HP 5890 Series II gas chromatograph interfaced with 5972 MSD. Chromatographic separation was achieved on HP-5MS fused silica capillary column (W&J 30 m 0.25 mm 0.5 mm) and helium 99.999 was used as a carrier gas (1 mL/min). Samples (volume 1 mL) were injected with an injection port temperature of 260 8C. The column oven temperature was programmed from initial temperature of 80 8C (2 min) at 20 8C/min to 200 8C (held for 2 min) then at 40 8C/min to 280 8C (held for 15 min). The detector temperature was 280 8C.
No.
Substance
Retention time
1 2 3 4 5 6 7 8 9 10 11 12
Amphetamine Methamphetamine Ephedrine Metronidazole Caffeine Theophylline Chlorphenamine Procaine Trimethoprim Chloroquine Quinine Fenethylline
6.50 7.00 8.40 10.00 10.90 11.40 11.60 11.80 16.00 16.50 20.02 20.65a
2.3. Sample preparation
a
Solid-phase extraction procedure was processed on all tablets and the extracts were analyzed by GC–MS using the conditions mentioned above. Ten milligrams of powdered tablet was added to 1 mL borate buffer at pH 9. The suspension was then sonicated for 15 min, centrifuged for 2 min at 4000 rpm and the supernatant was taken off. SPE procedure was carried out using IST C18 (130 mg) column. The SPE column was previously conditioned with 3 mL methanol, 3 mL deionized water and finally with 3 mL buffer. The prepared sample was then applied to the column at 1–2 mL/min. After drying for 2 min around 20 psi, the column was washed with 5 mL deionized water and dried again. The cartridge was eluted with 1 mL 2% ammonical ethyl acetate solution and evaporated to dryness under nitrogen below 40 8C. Extracts were reconstituted in 100 ml methanol. Two tablets from the same seizure were chosen at random and were analyzed for the purpose of establishing common origin. Each tablet was extracted, and analyzed separately to avoid cross contamination.
Data obtained from genuine tablet.
Fig. 1. GC–MS chromatogram of genuine captagon tablet.
tablets. Based on the analytical data obtained, apart from amphetamine and caffeine as the major constituents, several other substances were also detected in these so called captagon tablets (Table 1). Substances identified were not necessarily present in every tablet (Table 2). Fig. 1 shows the GC–MS chromatogram of genuine captagon tablet that contains fenethylline. Fenethylline, the active ingredient in captagon tablets, was not detected in all samples examined, although tablets have been marketed as such. Fig. 2
3. Results and discussion High sensitivity and specificity of GC–MS facilitated the identification of several potential substances in seized
Table 2 Potential substances detected in fourteen tablets as representatives of the total seized Samples
Amphetamine Methamphetamine Ephedrine Metronidazole Caffeine Theophylline Chlorphenamine Procaine Trimethoprim Chloroquine Quinine Fenethylline
Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample
D D D D D D D
1 2 3 4 5 6 7 8 9 10 11 12 13 14
D: detected.
D D
D D
D D
D D
D D D
D
D
D D D D
D D D
D
D
D D
D D
D
D D D
D D
D
D
M.A. Alabdalla / Forensic Science International 152 (2005) 185–188
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Fig. 2. GC–MS chromatogram of five (A–E) captagon tablets from five different seizures. Peaks identified are: (1) amphetamine, (2) methamphetamine, (3) ephedrine, (4) metronidazole, (5) caffeine, (6) theophylline, (7) chlorphenamine, (8) procaine, (9) trimethoprim (10) chloroquine and (11) quinine.
shows a comparison of chromatographic patterns of five samples from five different seizures. It is clear that they are different and consequently do not belong to a common batch. The data in Fig. 3 shows the comparison of two randomly
chosen tablets from the same seizure. It is confirmed that both samples are almost identical in their chromatographic patterns and are presumed to have been originated from the same batch. Amphetamine and methamphetamine detected
Fig. 3. GC–MS chromatogram of two (A and B) randomly chosen tablets from the same seizure. Peaks identified are: (1) amphetamine, (2) methamphetamine, (5) caffeine and (11) quinine.
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Table 3 Physiological activities of potential substances encountered in counterfeit captagons Substance
Physiological activity
Amphetamine Methamphetamine Ephedrine Metronidazole Caffeine Theophylline Chlorphenamine Procaine Trimethoprim Chloroquine Quinine Fenethylline
Stimulant Stimulant Sympathomemic Ant amebic Stimulant Vasodilator Antihistamine Local anesthetic Antibiotic Ant malarial Ant malarial Stimulant
4. Conclusion GC–MS in scanning mode is an excellent drug testing method. It provides sensitivity and selectivity, which makes it a method of choice for the present study. Analytical data obtained by GC–MS demonstrated that the majority of tablets contained one or more drugs capable of inducing effects similar to those of fenethylline, where as the genuine drug itself was absent in all samples examined. The comparison of chromatographic patterns is useful in establishing links between samples under investigation. Profound similarities of the so called ‘Signature Profiles’ support the assumption that samples could have been originated from the same batch or at least have been produced by the same manufacturer.
References in counterfeit captagon tablets are the main active drugs responsible for the stimulation effect experienced by abusers. Since these stimulants are controlled under the Dangerous Drug Ordinance in the laws of Jordan, assays of these substances are required in order to provide a reference to the court for sentency. Other potential substances identified in tested samples do not possess pharmacological activities similar to those of fenethylline, and their presence in combination with other drugs may contribute to the causes of health risks (Table 3).
[1] W. Keup, Use, indication and distribution in different countries of the stimulant and hallucinogenic amphetamine derivatives under consideration by WHO, Drug and Alcohol Dependence 17 (1986) 169–192. [2] Fenethylline and the Middle East. A brief summary. Drug Enforcement Administration, USA, 2003 DEA-03046. [3] N. Al-Gharably, A.R. Al-Obaid, The characterization of counterfeit captagon tablets, J. Forensic Sci. Soc. 34 (1994) 165–167. [4] S.R. Al-Hussaini, Counterfeit Captagon: an analytical study, J. Forensic Sci. Soc. 36 (1996) 139–142.
Chemical characterization of counterfeit captagon tablets seized in Jordan Mahmoud A. Alabdalla* Forensic Science Laboratory, Department of Chemical Analysis, P.O. Box: 330069, Amman 11134, Jordan Received 6 January 2004; received in revised form 6 August 2004; accepted 10 August 2004 Available online 1 October 2004
Abstract Fenethylline, commonly known by the trademark name ‘captagon’, is one of the most popular drugs of abuse among the young affluent communities of the Middle East. The Drug Control Department of the Public Security Directorate of Jordan has put captagon under control in the year 1988. Samples from 124 batches seized were analyzed by means of gas chromatograph– mass spectrometry (GC–MS). The analysis demonstrates the presence of amphetamine, caffeine and several other substances, besides, the absence of fenethylline. Based on GC–MS analytical data, comparisons were made between the various samples to determine the similarities and obtain inferences with respect to commonality of origin. # 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Counterfeit; Captagon; GC–MS; Tablets
1. Introduction Fenethylline, [7-(2-a-methylphenyl-aminoethyl)-theophylline], a synthetic-type stimulant, has become one of the most widely used illicit substances in the Middle East [1]. In the 1980s, the legal production of captagon tablets was ceased and the illicit production of the drug has increased [2]. Jordan is geographically located between drug producing countries to the north and drug consuming countries to the south and west. This has made, and continues to make Jordan a transient country for counterfeit captagon tablets. Although captagon is no longer in clinical use in Jordan since it’s banning in 1988, the country has witnessed a rise in the number of drug abusers. Investigators working on the characterization of counterfeit captagon tablets have directed their work to the use of ultraviolet (UV), infrared (IR) spectroscopic methods and thin layer chromatography (TLC) for the purpose of determining major active ingre* Tel.: +962 77 728758; fax: +962 6 5515119. E-mail address: [email protected].
dients present in these tablets [3,4]. GC–MS was chosen to identify as many potential substances as possible in counterfeit captagon tablets from different drug seizers. The chemical composition of each tablet was determined, and their chromatographic patterns were compared for the purpose of establishing links between different seizures.
2. Experimental 2.1. Materials and reagents One hundred and twenty-four batches of illicit captagon tablets seized by the Drug Control Authorities were received at different intervals. Each batch contained 5–15 tablets. Their chemical composition was compared with that of the legal standards available in the author’s laboratory. All reagents used where of analytical or HPLC grade. Solidphase extraction columns (ISOLUTE1) were supplied from International Sorbent Technology Ltd. Mid Glamorgan U.K.
0379-0738/$ – see front matter # 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.forsciint.2004.08.004
186
M.A. Alabdalla / Forensic Science International 152 (2005) 185–188
2.2. Gas chromatography
Table 1 Retention times of substances detected
GC–MS was carried out on HP 5890 Series II gas chromatograph interfaced with 5972 MSD. Chromatographic separation was achieved on HP-5MS fused silica capillary column (W&J 30 m 0.25 mm 0.5 mm) and helium 99.999 was used as a carrier gas (1 mL/min). Samples (volume 1 mL) were injected with an injection port temperature of 260 8C. The column oven temperature was programmed from initial temperature of 80 8C (2 min) at 20 8C/min to 200 8C (held for 2 min) then at 40 8C/min to 280 8C (held for 15 min). The detector temperature was 280 8C.
No.
Substance
Retention time
1 2 3 4 5 6 7 8 9 10 11 12
Amphetamine Methamphetamine Ephedrine Metronidazole Caffeine Theophylline Chlorphenamine Procaine Trimethoprim Chloroquine Quinine Fenethylline
6.50 7.00 8.40 10.00 10.90 11.40 11.60 11.80 16.00 16.50 20.02 20.65a
2.3. Sample preparation
a
Solid-phase extraction procedure was processed on all tablets and the extracts were analyzed by GC–MS using the conditions mentioned above. Ten milligrams of powdered tablet was added to 1 mL borate buffer at pH 9. The suspension was then sonicated for 15 min, centrifuged for 2 min at 4000 rpm and the supernatant was taken off. SPE procedure was carried out using IST C18 (130 mg) column. The SPE column was previously conditioned with 3 mL methanol, 3 mL deionized water and finally with 3 mL buffer. The prepared sample was then applied to the column at 1–2 mL/min. After drying for 2 min around 20 psi, the column was washed with 5 mL deionized water and dried again. The cartridge was eluted with 1 mL 2% ammonical ethyl acetate solution and evaporated to dryness under nitrogen below 40 8C. Extracts were reconstituted in 100 ml methanol. Two tablets from the same seizure were chosen at random and were analyzed for the purpose of establishing common origin. Each tablet was extracted, and analyzed separately to avoid cross contamination.
Data obtained from genuine tablet.
Fig. 1. GC–MS chromatogram of genuine captagon tablet.
tablets. Based on the analytical data obtained, apart from amphetamine and caffeine as the major constituents, several other substances were also detected in these so called captagon tablets (Table 1). Substances identified were not necessarily present in every tablet (Table 2). Fig. 1 shows the GC–MS chromatogram of genuine captagon tablet that contains fenethylline. Fenethylline, the active ingredient in captagon tablets, was not detected in all samples examined, although tablets have been marketed as such. Fig. 2
3. Results and discussion High sensitivity and specificity of GC–MS facilitated the identification of several potential substances in seized
Table 2 Potential substances detected in fourteen tablets as representatives of the total seized Samples
Amphetamine Methamphetamine Ephedrine Metronidazole Caffeine Theophylline Chlorphenamine Procaine Trimethoprim Chloroquine Quinine Fenethylline
Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample Sample
D D D D D D D
1 2 3 4 5 6 7 8 9 10 11 12 13 14
D: detected.
D D
D D
D D
D D
D D D
D
D
D D D D
D D D
D
D
D D
D D
D
D D D
D D
D
D
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Fig. 2. GC–MS chromatogram of five (A–E) captagon tablets from five different seizures. Peaks identified are: (1) amphetamine, (2) methamphetamine, (3) ephedrine, (4) metronidazole, (5) caffeine, (6) theophylline, (7) chlorphenamine, (8) procaine, (9) trimethoprim (10) chloroquine and (11) quinine.
shows a comparison of chromatographic patterns of five samples from five different seizures. It is clear that they are different and consequently do not belong to a common batch. The data in Fig. 3 shows the comparison of two randomly
chosen tablets from the same seizure. It is confirmed that both samples are almost identical in their chromatographic patterns and are presumed to have been originated from the same batch. Amphetamine and methamphetamine detected
Fig. 3. GC–MS chromatogram of two (A and B) randomly chosen tablets from the same seizure. Peaks identified are: (1) amphetamine, (2) methamphetamine, (5) caffeine and (11) quinine.
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Table 3 Physiological activities of potential substances encountered in counterfeit captagons Substance
Physiological activity
Amphetamine Methamphetamine Ephedrine Metronidazole Caffeine Theophylline Chlorphenamine Procaine Trimethoprim Chloroquine Quinine Fenethylline
Stimulant Stimulant Sympathomemic Ant amebic Stimulant Vasodilator Antihistamine Local anesthetic Antibiotic Ant malarial Ant malarial Stimulant
4. Conclusion GC–MS in scanning mode is an excellent drug testing method. It provides sensitivity and selectivity, which makes it a method of choice for the present study. Analytical data obtained by GC–MS demonstrated that the majority of tablets contained one or more drugs capable of inducing effects similar to those of fenethylline, where as the genuine drug itself was absent in all samples examined. The comparison of chromatographic patterns is useful in establishing links between samples under investigation. Profound similarities of the so called ‘Signature Profiles’ support the assumption that samples could have been originated from the same batch or at least have been produced by the same manufacturer.
References in counterfeit captagon tablets are the main active drugs responsible for the stimulation effect experienced by abusers. Since these stimulants are controlled under the Dangerous Drug Ordinance in the laws of Jordan, assays of these substances are required in order to provide a reference to the court for sentency. Other potential substances identified in tested samples do not possess pharmacological activities similar to those of fenethylline, and their presence in combination with other drugs may contribute to the causes of health risks (Table 3).
[1] W. Keup, Use, indication and distribution in different countries of the stimulant and hallucinogenic amphetamine derivatives under consideration by WHO, Drug and Alcohol Dependence 17 (1986) 169–192. [2] Fenethylline and the Middle East. A brief summary. Drug Enforcement Administration, USA, 2003 DEA-03046. [3] N. Al-Gharably, A.R. Al-Obaid, The characterization of counterfeit captagon tablets, J. Forensic Sci. Soc. 34 (1994) 165–167. [4] S.R. Al-Hussaini, Counterfeit Captagon: an analytical study, J. Forensic Sci. Soc. 36 (1996) 139–142.