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Forensic Toxicology

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19.09.2018 | Original Article

Simultaneous determination of selegiline, desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine in oral fluid by LC/MS/MS

verfasst von: Lizhu Chen, Yingjia Yu, Yang Wang, Ping Xiang, Gengli Duan

Erschienen in: Forensic Toxicology | Ausgabe 1/2019

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Abstract

Purpose

It is crucial for forensic analysis to differentiate clinical use from illegal abuse. Selegiline (SG) is mainly metabolized to desmethylselegiline (DM-SG), R-(−)-methamphetamine (R-MA) and R-(−)amphetamine (R-AM); while abused methamphetamine and amphetamine mainly contain the S-(+)-form. The aim of this study was to simultaneously determine SG, DM-SG, R/S-MA, and R/S-AM in human oral fluid (OF) and to differentiate clinical use from illegal use. We also aim to apply the present method to the OF samples from authentic cases in forensic toxicology.

Methods

Liquid–liquid extraction and liquid chromatography-tandem mass spectrometry operating in positive ion multiple-reaction monitoring mode were utilized. The chromatographic system consisted of a Chirobiotic^TM V2 column (2.1 mm × 250 mm, 5 μm) and a mobile phase of methanol containing 0.1% (v/v) glacial acetic acid and 0.02% (v/v) ammonium hydroxide.

Results and conclusions

The calibration curves were linear from 1 to 100 ng/mL, and r > 0.995 for all analytes with imprecisions ≤ 15% and accuracy between 85 and 115%. Extraction recoveries ranged from 46.3 to 104.7% with coefficient of variation (CV) ≤ 10.3% and matrix effects (MEs) ranged from 47.4 to 114.8% with CV ≤ 12.9%. The lower limit of quantification was 0.2 ng/mL for SG and DM-SG and 1.0 ng/mL for S-MA, R-MA, S-AM and R-AM. The present method is simple, rapid (accomplished in 12 min), sensitive, and validated by authentic samples.

Cone EJ, Huestis MA (2007) Interpretation of oral fluid tests for drugs of abuse. Ann N Y Acad Sci 1098:51–103. https://doi.org/10.1196/annals.1384.037 CrossRefPubMedPubMedCentral

Bosker WM, Huestis MA (2009) Oral fluid testing for drugs of abuse. Clin Chem 55(11):1910–1931. https://doi.org/10.1373/clinchem.2008.108670 CrossRefPubMedPubMedCentral

Heltsley R, DePriest A, Black DL, Robert T, Marshall L, Meadors VM, Caplan YH, Cone EJ (2011) Oral fluid drug testing of chronic pain patients. I. Positive prevalence rates of licit and illicit drugs. J Anal Toxicol 35(8):529–540CrossRefPubMed

Chu M, Gerostamoulos D, Beyer J, Rodda L, Boorman M, Drummer OH (2012) The incidence of drugs of impairment in oral fluid from random roadside testing. Forensic Sci Int 215(1–3):28–31. https://doi.org/10.1016/j.forsciint.2011.05.012 CrossRefPubMed

Bush DM (2008) The US mandatory guidelines for federal workplace drug testing programs: current status and future considerations. Forensic Sci Int 174(2–3):111–119. https://doi.org/10.1016/j.forsciint.2007.03.008 CrossRefPubMed

Huestis MA, Cone EJ (2004) Relationship of Delta 9-tetrahydrocannabinol concentrations in oral fluid and plasma after controlled administration of smoked cannabis. J Anal Toxicol 28(6):394–399CrossRefPubMed

Mohamed KM, Al-Hazmi AH, Alasiri AM, Ali Mel S (2016) A GC-MS Method for Detection and Quantification of Cathine, Cathinone, Methcathinone and Ephedrine in Oral Fluid. J Chromatogr Sci 54(8):1271–1276. https://doi.org/10.1093/chromsci/bmw082 CrossRefPubMed

Newmeyer MN, Concheiro M, da Costa JL, Flegel R, Gorelick DA, Huestis MA (2015) Oral fluid with three modes of collection and plasma methamphetamine and amphetamine enantiomer concentrations after controlled intranasal l-methamphetamine administration. Drug Test Anal 7(10):877–883. https://doi.org/10.1002/dta.1784 CrossRefPubMedPubMedCentral

Clarke A, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH (2003) A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition. J Neural Transm (Vienna) 110(11):1241–1255. https://doi.org/10.1007/s00702-003-0036-4 CrossRef

10.

Katagi M, Tatsuno M, Miki A, Nishikawa M, Nakajima K, Tsuchihashi H (2001) Simultaneous determination of selegiline-N-oxide, a new indicator for selegiline administration, and other metabolites in urine by high-performance liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr B Biomed Sci Appl 759(1):125–133CrossRefPubMed

11.

Salonen JS, Nyman L, Boobis AR, Edwards RJ, Watts P, Lake BG, Price RJ, Renwick AB, Gomez-Lechon MJ, Castell JV, Ingelman-Sundberg M, Hidestrand M, Guillouzo A, Corcos L, Goldfarb PS, Lewis DF, Taavitsainen P, Pelkonen O (2003) Comparative studies on the cytochrome p450-associated metabolism and interaction potential of selegiline between human liver-derived in vitro systems. Drug Metab Dispos 31(9):1093–1102. https://doi.org/10.1124/dmd.31.9.1093 CrossRefPubMed

12.

Siu EC, Tyndale RF (2008) Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice. J Pharmacol Exp Ther 324(3):992–999. https://doi.org/10.1124/jpet.107.133900 CrossRefPubMed

13.

Wurita A, Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Suzuki O, Watanabe K (2016) Postmortem redistribution of methamphetamine and amphetamine in blood specimens from various blood vessels and in the specimens from pericardial fluid, bile, stomach contents and various solid tissues collected from a human cadaver. Forensic Toxicol 34(1):191–198. https://doi.org/10.1007/s11419-015-0303-8 CrossRef

14.

Makino Y, Suzuki A, Ogawa T, Shirota O (1999) Direct determination of methamphetamine enantiomers in urine by liquid chromatography with a strong cation-exchange precolumn and phenyl-beta-cyclodextrin-bonded semi-microcolumn. J Chromatogr B Biomed Sci Appl 729(1–2):97–101CrossRefPubMed

15.

Maurer HH, Kraemer T (1992) Toxicological detection of selegiline and its metabolites in urine using fluorescence polarization immunoassay (FPIA) and gas chromatography-mass spectrometry (GC-MS) and differentiation by enantioselective GC-MS of the intake of selegiline from abuse of methamphetamine or amphetamine. Arch Toxicol 66(9):675–678CrossRefPubMed

16.

Liu Y, Hao B, Shi Y, Xue L, Wang X, Chen Y, Zhao H (2017) Violent offences of methamphetamine users and dilemmas of forensic psychiatric assessment. Forensic Sci Res 2(1):11–17CrossRefPubMedPubMedCentral

17.

Reimer ML, Mamer OA, Zavitsanos AP, Siddiqui AW, Dadgar D (1993) Determination of amphetamine, methamphetamine and desmethyldeprenyl in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry. Biol Mass Spectrom 22(4):235–242. https://doi.org/10.1002/bms.1200220404 CrossRefPubMed

18.

Heinonen EH, Anttila MI, Lammintausta RA (1994) Pharmacokinetic aspects of l-deprenyl (selegiline) and its metabolites. Clin Pharmacol Ther 56(6 Pt 2):742–749CrossRefPubMed

19.

Esposito FM, Crumpton S, Mitchell J, Flegel RR (2012) Evaluation of the 20% D-methamphetamine requirement for determining illicit use of methamphetamine in urine. J Anal Toxicol 36(6):399–404. https://doi.org/10.1093/jat/bks042 CrossRefPubMed

20.

Mohr S, Weiss JA, Spreitz J, Schmid MG (2012) Chiral separation of new cathinone- and amphetamine-related designer drugs by gas chromatography-mass spectrometry using trifluoroacetyl-l-prolyl chloride as chiral derivatization reagent. J Chromatogr A 1269:352–359. https://doi.org/10.1016/j.chroma.2012.09.079 CrossRefPubMed

21.

Segawa H, Iwata YT, Yamamuro T, Kuwayama K, Tsujikawa K, Kanamori T, Inoue H (2017) Enantioseparation of methamphetamine by supercritical fluid chromatography with cellulose-based packed column. Forensic Sci Int 273:39–44. https://doi.org/10.1016/j.forsciint.2017.01.025 CrossRefPubMed

22.

Sevcik J, Stransky Z, Ingelse BA, Lemr K (1996) Capillary electrophoretic enantioseparation of selegiline, methamphetamine and ephedrine using a neutral beta-cyclodextrin epichlorhydrin polymer. J Pharm Biomed Anal 14(8–10):1089–1094CrossRefPubMed

23.

Weiss JA, Kadkhodaei K, Schmid MG (2017) Indirect chiral separation of 8 novel amphetamine derivatives as potential new psychoactive compounds by GC-MS and HPLC. Sci Justice 57(1):6–12. https://doi.org/10.1016/j.scijus.2016.08.007 CrossRefPubMed

24.

Hadener M, Bruni PS, Weinmann W, Frubis M, Konig S (2017) Accelerated quantification of amphetamine enantiomers in human urine using chiral liquid chromatography and on-line column-switching coupled with tandem mass spectrometry. Anal Bioanal Chem 409(5):1291–1300. https://doi.org/10.1007/s00216-016-0056-1 CrossRefPubMed

25.

Wang T, Shen B, Shi Y, Xiang P, Yu Z (2015) Chiral separation and determination of R/S-methamphetamine and its metabolite R/S-amphetamine in urine using LC-MS/MS. Forensic Sci Int 246:72–78. https://doi.org/10.1016/j.forsciint.2014.11.009 CrossRefPubMed

26.

Kronstrand R, Ahlner J, Dizdar N, Larson G (2003) Quantitative analysis of desmethylselegiline, methamphetamine, and amphetamine in hair and plasma from Parkinson patients on long-term selegiline medication. J Anal Toxicol 27(3):135–141CrossRefPubMed

27.

Nishida K, Itoh S, Inoue N, Kudo K, Ikeda N (2006) High-performance liquid chromatographic-mass spectrometric determination of methamphetamine and amphetamine enantiomers, desmethylselegiline and selegiline, in hair samples of long-term methamphetamine abusers or selegiline users. J Anal Toxicol 30(4):232–237CrossRefPubMed

28.

Leis HJ, Fauler G, Windischhofer W (2014) Enantioselective quantitative analysis of amphetamine in human plasma by liquid chromatography/high-resolution mass spectrometry. Anal Bioanal Chem 406(18):4473–4480. https://doi.org/10.1007/s00216-014-7850-4 CrossRefPubMed

29.

Borg D, Kolb E, Lantigua C, Stripp R (2018) Chiral analysis of methamphetamine in oral fluid samples: a method to distinguish licit from illicit drug use. J Anal Toxicol 42(1):25–32. https://doi.org/10.1093/jat/bkx079 CrossRefPubMed

30.

Newmeyer MN, Concheiro M, Huestis MA (2014) Rapid quantitative chiral amphetamines liquid chromatography-tandem mass spectrometry: method in plasma and oral fluid with a cost-effective chiral derivatizing reagent. J Chromatogr A 1358:68–74. https://doi.org/10.1016/j.chroma.2014.06.096 CrossRefPubMedPubMedCentral

31.

Malakova J, Pavek P, Svecova L, Jokesova I, Zivny P, Palicka V (2009) New high-performance liquid chromatography method for the determination of (R)-warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase. J Chromatogr B Analyt Technol Biomed Life Sci 877(27):3226–3230. https://doi.org/10.1016/j.jchromb.2009.07.009 CrossRefPubMed

32.

Alyamani M, Li Z, Upadhyay SK, Anderson DJ, Auchus RJ, Sharifi N (2017) Development and validation of a novel LC-MS/MS method for simultaneous determination of abiraterone and its seven steroidal metabolites in human serum: innovation in separation of diastereoisomers without use of a chiral column. J Steroid Biochem Mol Biol 172:231–239. https://doi.org/10.1016/j.jsbmb.2016.04.002 CrossRefPubMed

33.

Yu J, Tang J, Yuan X, Guo X, Zhao L (2017) Evaluation of the chiral recognition properties and the column performances of three chiral stationary phases based on cellulose for the enantioseparation of six dihydropyridines by high-performance liquid chromatography. Chirality 29(3–4):147–154. https://doi.org/10.1002/chir.22690 CrossRefPubMed

34.

Ribeiro AR, Maia AS, Cass QB, Tiritan ME (2014) Enantioseparation of chiral pharmaceuticals in biomedical and environmental analyses by liquid chromatography: an overview. J Chromatogr B Analyt Technol Biomed Life Sci 968:8–21. https://doi.org/10.1016/j.jchromb.2014.02.049 CrossRefPubMed

35.

Azzaro AJ, Ziemniak J, Kemper E, Campbell BJ, VanDenBerg C (2007) Pharmacokinetics and absolute bioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules. J Clin Pharmacol 47(10):1256–1267. https://doi.org/10.1177/0091270007304779 CrossRefPubMed

36.

Kronstrand R, Andersson MC, Ahlner J, Larson G (2001) Incorporation of selegiline metabolites into hair after oral selegiline intake. J Anal Toxicol 25(7):594–601CrossRefPubMed

Titel: Simultaneous determination of selegiline, desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine in oral fluid by LC/MS/MS
verfasst von: Lizhu Chen
Yingjia Yu
Yang Wang
Ping Xiang
Gengli Duan
Publikationsdatum: 19.09.2018
Verlag: Springer Japan
Erschienen in: Forensic Toxicology / Ausgabe 1/2019
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-018-0443-8

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