Analytical Toxicology of Emerging Drugs of Abuse

The emergence of ever new drugs of abuse on the illicit drug market is an ongoing challenge for analytical toxicologists. Because most of these new drugs or drug classes are not detected by established analytical methods targeting classic drugs of abuse, analytical procedures must be adapted or new procedures must be developed to cover these new compounds. This review summarizes the analytical toxicology of the following classes of emerging drugs of abuse: piperazines, phenethylamines (2Cs and FLYs), 4-substituted amphetamines, β-keto-amphetamines, 2,5-dimethoxy-amphetamines, pyrrolidinophenones, and synthetic cannabinoids.

[1]  N. Ferreirós,et al.  'Spice' and other herbal blends: harmless incense or cannabinoid designer drugs? , 2009, Journal of mass spectrometry : JMS.

[2]  S. van Calenbergh,et al.  Fatality due to combined use of the designer drugs MDMA and PMA: a distribution study. , 2003, Journal of analytical toxicology.

[3]  J. Röhrich,et al.  A fatal paramethoxymethamphetamine intoxication. , 2003, Legal medicine.

[4]  Yasushige Mori,et al.  Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. , 2009, Forensic science international.

[5]  H. Maurer,et al.  Studies on the metabolism and toxicological detection of the designer drug 4-ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E) in rat urine using gas chromatographic-mass spectrometric techniques. , 2006, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[6]  Frank T Peters,et al.  Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography–mass spectrometry , 2010, Analytical and bioanalytical chemistry.

[7]  H. Maurer,et al.  Metabolism and toxicological detection of the new designer drug 3',4'-methylenedioxy-alpha-pyrrolidinopropiophenone studied in urine using gas chromatography-mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[8]  H. Maurer,et al.  Studies on the Human Metabolism and the Toxicologic Detection of the Cough Suppressant Dropropizine in Urine Using Gas Chromatography-Mass Spectrometry , 2004, Therapeutic drug monitoring.

[9]  Metabolism and toxicological detection of the designer drug 4-chloro-2,5-dimethoxyamphetamine in rat urine using gas chromatography-mass spectrometry , 2008, Analytical and bioanalytical chemistry.

[10]  H. Maurer,et al.  Metabolism of the new designer drug alpha-pyrrolidinopropiophenone (PPP) and the toxicological detection of PPP and 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP) studied in rat urine using gas chromatography-mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[11]  K. Kuwayama,et al.  In vivo metabolism of 2,5-dimethoxy-4-propylthiophenethylamine in rat , 2007, Xenobiotica; the fate of foreign compounds in biological systems.

[12]  F. Peters,et al.  Studies on the metabolism and toxicological detection of the new designer drug 4'-methyl-α-pyrrolidinopropiophenone in urine using gas chromatography-mass spectrometry , 2002 .

[13]  M. Balíková Nonfatal and fatal DOB (2,5-dimethoxy-4-bromoamphetamine) overdose. , 2005, Forensic science international.

[14]  P. Kemp,et al.  Postmortem identification and quantitation of 2,5-dimethoxy-4-n-propylthiophenethylamine using GC-MSD and GC-NPD. , 2003, Journal of analytical toxicology.

[15]  J. Sklerov,et al.  A general screening and confirmation approach to the analysis of designer tryptamines and phenethylamines in blood and urine using GC-EI-MS and HPLC-electrospray-MS. , 2004, Journal of analytical toxicology.

[16]  R. de la Torre,et al.  Liquid chromatography-atmospheric pressure ionization electrospray mass spectrometry determination of "hallucinogenic designer drugs" in urine of consumers. , 2008, Journal of pharmaceutical and biomedical analysis.

[17]  H. Maurer,et al.  New designer drug, 2,5-dimethoxy-4-propylthio-beta-phenethylamine (2C-T-7): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry. , 2005, Journal of mass spectrometry : JMS.

[18]  Frank T Peters,et al.  Studies on the metabolism and toxicological detection of the designer drug 4-methylthioamphetamine (4-MTA) in human urine using gas chromatography-mass spectrometry. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[19]  O. Beck,et al.  Application of direct urine LC-MS-MS analysis for screening of novel substances in drug abusers. , 2005, Journal of analytical toxicology.

[20]  M. Nishikawa,et al.  Development of simultaneous gas chromatography-mass spectrometric and liquid chromatography-electrospray ionization mass spectrometric determination method for the new designer drugs, N-benzylpiperazine (BZP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP) and their main metabolites in urine. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[21]  H. Yin,et al.  Recent paramethoxymethamphetamine (PMMA) deaths in Taiwan. , 2007, Journal of analytical toxicology.

[22]  H. Maurer,et al.  Toxicological detection of the new designer drug 1-(4-methoxyphenyl)piperazine and its metabolites in urine and differentiation from an intake of structurally related medicaments using gas chromatography-mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[23]  G. Boatto,et al.  Determination of 4-alkyl 2,5 dimethoxy-amphetamine derivatives by capillary electrophoresis with mass spectrometry detection from urine samples. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[24]  H. Maurer,et al.  New designer drug 1-(3,4-methylenedioxybenzyl) piperazine (MDBP): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry. , 2004, Journal of mass spectrometry : JMS.

[25]  J. Laurens,et al.  Rapid GC-MS confirmation of amphetamines in urine by extractive acylation. , 2009, Forensic science international.

[26]  H. Maurer,et al.  Studies on the metabolism and the toxicological analysis of the nootropic drug fipexide in rat urine using gas chromatography-mass spectrometry. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[27]  F. Peters,et al.  Screening for and validated quantification of phenethylamine-type designer drugs and mescaline in human blood plasma by gas chromatography/mass spectrometry. , 2005, Journal of mass spectrometry : JMS.

[28]  F. Peters,et al.  Screening for and validated quantification of amphetamines and of amphetamine- and piperazine-derived designer drugs in human blood plasma by gas chromatography/mass spectrometry. , 2003, Journal of mass spectrometry : JMS.

[29]  M. Marchetti,et al.  LC-MS analysis of trimethoxyamphetamine designer drugs (TMA series) from urine samples. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[30]  T. L. Martin Three cases of fatal paramethoxyamphetamine overdose. , 2001, Journal of analytical toxicology.

[31]  Designer drug 2,4,5-trimethoxyamphetamine (TMA-2): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. , 2006, Journal of mass spectrometry : JMS.

[32]  F. Peters,et al.  New designer drug 4'-methyl-alpha-pyrrolidinohexanophenone: studies on its metabolism and toxicological detection in urine using gas chromatography-mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[33]  M. Andreasen,et al.  A fatal poisoning involving Bromo-Dragonfly. , 2009, Forensic science international.

[34]  H. Maurer,et al.  Metabolism and toxicological detection of the new designer drug 4'-methoxy-alpha-pyrrolidinopropiophenone studied in rat urine using gas chromatography-mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[35]  W. Lambert,et al.  Fatal 4-MTA intoxication: development of a liquid chromatographic-tandem mass spectrometric assay for multiple matrices. , 2001, Journal of analytical toxicology.

[36]  H. Maurer,et al.  On the metabolism of the amphetamine-derived antispasmodic drug mebeverine: gas chromatography-mass spectrometry studies on rat liver microsomes and on human urine. , 2000, Drug metabolism and disposition: the biological fate of chemicals.

[37]  E. Baralla,et al.  Multi-residue analysis of eight thioamphetamine designer drugs in human urine by liquid chromatography/tandem mass spectrometry. , 2009, Rapid communications in mass spectrometry : RCM.

[38]  K. Kudo,et al.  Simultaneous determination of 13 amphetamine related drugs in human whole blood using an enhanced polymer column and gas chromatography-mass spectrometry. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[39]  H. Maurer,et al.  Studies on the metabolism and toxicological detection of the designer drug 2,5‐dimethoxy‐4‐methyl‐β‐ phenethylamine (2C‐D) in rat urine using gas chromatographic/mass spectrometric techniques , 2006 .

[40]  H. Maurer,et al.  Screening for Detection of New Antidepressants, Neuroleptics, Hypnotics, and Their Metabolites in Urine by GC-MS Developed Using Rat Liver Microsomes , 2001, Therapeutic drug monitoring.

[41]  M. Pütz,et al.  New designer drug 4-iodo-2,5-dimethoxy-beta-phenethylamine (2C-I): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric and capillary electrophoretic/mass spectrometric techniques. , 2006, Journal of mass spectrometry : JMS.

[42]  Ryoji Matoba,et al.  Determination of a newly encountered designer drug "p-methoxyethylamphetamine" and its metabolites in human urine and blood. , 2008, Forensic science international.

[43]  G. Boatto,et al.  Determination of four thiophenethylamine designer drugs (2C-T-series) in human plasma by capillary electrophoresis with mass spectrometry detection. , 2007, Journal of chromatography. A.

[44]  S. Elliott Fatal poisoning with a new phenylethylamine: 4-methylthioamphetamine (4-MTA). , 2000, Journal of analytical toxicology.

[45]  H. Maurer,et al.  New designer drug 1-(3-trifluoromethylphenyl) piperazine (TFMPP): gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry studies on its phase I and II metabolism and on its toxicological detection in rat urine. , 2003, Journal of mass spectrometry : JMS.

[46]  K. Tsujikawa,et al.  Excretory Profile of 4-Bromo-2,5-dimethoxy-phenethylamine (2C-B) in Rat , 2003 .

[47]  J. Kraner,et al.  Fatalities caused by the MDMA-related drug paramethoxyamphetamine (PMA). , 2001, Journal of analytical toxicology.

[48]  Michael Puetz,et al.  New designer drug 2,5-dimethoxy-4-ethylthio-beta-phenethylamine (2C-T-2): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry. , 2005, Journal of mass spectrometry : JMS.

[49]  T. Kanamori,et al.  In vivo metabolism of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) in the rat: identification of urinary metabolites. , 2002, Journal of analytical toxicology.

[50]  H. Maurer,et al.  Studies on the toxicological detection of the designer drug 4-bromo-2,5-dimethoxy-beta-phenethylamine (2C-B) in rat urine using gas chromatography-mass spectrometry. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[51]  H. Inoue,et al.  Metabolism and the urinary excretion profile of the recently scheduled designer drug N-Benzylpiperazine (BZP) in the rat. , 2006, Journal of analytical toxicology.

[52]  H. Maurer,et al.  Metabolism and toxicological detection of the designer drug 4-iodo-2,5-dimethoxy-amphetamine (DOI) in rat urine using gas chromatography-mass spectrometry. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[53]  M. Franzmann,et al.  Three fatal cases of PMA and PMMA poisoning in Denmark. , 2003, Journal of analytical toxicology.

[54]  M. Nishikawa,et al.  Metabolism of the recently encountered designer drug, methylone, in humans and rats , 2006, Xenobiotica; the fate of foreign compounds in biological systems.

[55]  H. Maurer,et al.  Abuse of Nutmeg (Myristica fragrans Houtt.): Studies on the Metabolism and the Toxicologic Detection of its Ingredients Elemicin, Myristicin, and Safrole in Rat and Human Urine Using Gas Chromatography/Mass Spectrometry , 2006, Therapeutic drug monitoring.

[56]  Cheng-Huang Lin,et al.  The bioactivity of 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2) and its detection in rat urine by capillary electrophoresis combined with an on-line sample concentration technique. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[57]  H. Inoue,et al.  Isolation, identification and excretion profile of the principal urinary metabolite of the recently banned designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rats , 2005, Xenobiotica; the fate of foreign compounds in biological systems.

[58]  D. Davoudzadeh,et al.  Multiplex assay of amphetamine, methamphetamine, and ecstasy drug using CEDIA technology. , 2002, Journal of analytical toxicology.

[59]  Michael Puetz,et al.  Designer drug 2,5-dimethoxy-4-methyl-amphetamine (DOM, STP): involvement of the cytochrome P450 isoenzymes in formation of its main metabolite and detection of the latter in rat urine as proof of a drug intake using gas chromatography-mass spectrometry. , 2008, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[60]  Christopher Smith,et al.  Investigation of the first deaths in the United Kingdom involving the detection and quantitation of the piperazines BZP and 3-TFMPP. , 2008, Journal of analytical toxicology.

[61]  H. Maurer,et al.  Designer drugs 2,5-dimethoxy-4-bromo-amphetamine (DOB) and 2,5-dimethoxy-4-bromo-methamphetamine (MDOB): studies on their metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. , 2006, Journal of mass spectrometry : JMS.

[62]  H. Maurer,et al.  Studies on the metabolism and toxicological detection of the designer drug 2,5-dimethoxy-4-methyl-beta- phenethylamine (2C-D) in rat urine using gas chromatographic/mass spectrometric techniques. , 2006, Journal of mass spectrometry : JMS.

[63]  I. Bosman,et al.  Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market. , 2001, Forensic science international.

[64]  I. Bosman,et al.  More data about the new psychoactive drug 2C-B. , 1999, Journal of Analytical Toxicology.

[65]  H. Maurer,et al.  New designer drug p-methoxymethamphetamine: studies on its metabolism and toxicological detection in urine using gas chromatography-mass spectrometry. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[66]  J. Kyd,et al.  Matrix effect and cross-reactivity of select amphetamine-type substances, designer analogues, and putrefactive amines using the Bio-Quant direct ELISA presumptive assays for amphetamine and methamphetamine. , 2007, Journal of analytical toxicology.

[67]  Karl Pfleger,et al.  Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites: Part 3 mass spectra (m/z222 to 777 amu). , 1992 .

[68]  S. van Calenbergh,et al.  Determination of paramethoxyamphetamine and other amphetamine-related designer drugs by liquid chromatography/sonic spray ionization mass spectrometry. , 2002, Rapid communications in mass spectrometry : RCM.

[69]  H. Maurer,et al.  Studies on the metabolism and toxicological detection of the new designer drug N-benzylpiperazine in urine using gas chromatography-mass spectrometry. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[70]  H. Maurer,et al.  Piperazine-derived designer drug 1-(3-chlorophenyl)piperazine (mCPP): GC-MS studies on its metabolism and its toxicological detection in rat urine including analytical differentiation from its precursor drugs trazodone and nefazodone. , 2003, Journal of analytical toxicology.

[71]  B. Levine,et al.  Detection of 1-benzylpiperazine and 1-(3-trifluoromethylphenyl)-piperazine in urine analysis specimens using GC-MS and LC-ESI-MS. , 2008, Journal of analytical toxicology.

[72]  A. Verstraete,et al.  Acute Chlorophenylpiperazine Overdose: A Case Report and Review of the Literature , 2008, Therapeutic drug monitoring.