nach oben

Forensic Toxicology

Erschienen in:

28.03.2022 | Original Article

Chiral analysis of dextromethorphan and levomethorphan in human hair by liquid chromatography–tandem mass spectrometry

verfasst von: Jiao-jiao Ji, Junbo Zhao, Ping Xiang, Hui Yan, Min Shen

Erschienen in: Forensic Toxicology | Ausgabe 2/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Methorphan exists in two enantiomeric forms including dextromethorphan and levomethorphan. Dextromethorphan is an over-the-counter antitussive drug, whereas levomethorphan is strictly controlled as a narcotic drug. Chiral analysis of methorphan could, therefore, assist clinicians and forensic experts in differentiating between illicit and therapeutic use and in tracing the source of the drug.

Methods

A method for enantiomeric separation and quantification of levomethorphan and dextromethorphan in human hair was developed and validated using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Hair was extracted in hydrochloric acid/methanol (1:20, v/v). The supernatant were separated using a Supelco Astec Chirobiotic™ V2 column (250 × 2.1 mm, i.d., 5 μm particle size) and analyzed on a triple quadrupole linear ion trap mass spectrometer in multiple reaction monitoring mode.

Results

The limits of detection for dextromethorphan and levomethorphan were 2 and 1 pg/mg, respectively; the lower limit of quantification was 2 pg/mg for both drugs. Good linearity (r > 0.995) was observed for both analytes over the linear range. Precision values were below 10% for both analytes; accuracy values ranged from 87.5 to 101%. The extraction recoveries were 78.3–98.4%, and matrix effects were 70.5–88.6%. This method was applied to human hair samples from 120 people suspected of methorphan use to further distinguish the drug chirality. Dextromethorphan was detected in all 120 samples at a concentration range of 2.7–19,100 pg/mg, whereas levomethorphan was not detected in any sample.

Conclusions

A sensitive quantitative method was established for the enantiomeric separation of dextromethorphan and levomethorphan in hair. This is the first study to achieve chiral analysis of methorphan in human hair.

Ford JA (2009) Misuse of over-the-counter cough or cold medications among adolescents: prevalence and correlates in a national sample. J Adolesc Health 44:505–507. https://doi.org/10.1016/j.jadohealth.2008.10.140CrossRefPubMed

Mutschler J, Koopmann A, Grosshans M, Hermann D, Mann K, Kiefer F (2010) Dextromethorphan withdrawal and dependence syndrome. Dtsch Arztebl Int 107:537–540. https://doi.org/10.3238/arztebl.2010.0537 (open access article)CrossRefPubMedPubMedCentral

Bryner JK, Wang UK, Hui JW, Bedodo M, MacDougall C, Anderson IB (2006) Dextromethorphan abuse in adolescence. Arch Pediatr Adolesc Med 160:1217–1222. https://doi.org/10.1001/archpedi.160.12.1217CrossRefPubMedPubMedCentral

Logan BK, Gary G, Rebecca H, James K (2009) Five deaths resulting from abuse of dextromethorphan sold over the Internet. J Anal Toxicol 33:99–103. https://doi.org/10.1093/jat/33.2.99CrossRefPubMed

Rammer L, Holmgren P, Sandler H (1988) Fatal intoxication by dextromethorphan: a report on two cases. Forensic Sci Int 37:233–236. https://doi.org/10.1016/0379-0738(88)90230-7CrossRefPubMed

Chyka PA, Erdman AR, Manoguerra AS, Christianson G, Booze LL, Nelson LS, Woolf AD, Cobaugh DJ, Caravati EM, Scharman EJ, Troutman WG (2007) Dextromethorphan poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol 45:662–677. https://doi.org/10.1080/15563650701606443 (open access article)CrossRef

Modi D, Bhalavat R, Patterson JC (2013) Suicidal and homicidal behaviors related to dextromethorphan abuse in a middle-aged woman. J Addict Med 7:143–144. https://doi.org/10.1097/ADM.0b013e318281a547CrossRefPubMed

Reissig CJ, Carter LP, Johnson MW, Mintzer MZ, Klinedinst MA, Griffiths RR (2012) High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens. Psychopharmacology 223:1–15. https://doi.org/10.1007/s00213-012-2680-6CrossRefPubMedPubMedCentral

Bortolotti F, Bertaso A, Gottardo R, Musile G, Tagliaro F (2013) Dextromethorphan/levomethorphan issues in a case of opiate overdose. Drug Test Anal 5:781–784. https://doi.org/10.1002/dta.1577CrossRefPubMed

10.

International Narcotics Control Board (2011) List of narcotic drugs under international control. https://www.incb.org/documents/Narcotic-Drugs/Yellow_List/NAR_2011_YellowList_50edition_EN.pdf. Accessed Dec 2011

11.

Lin S-Y, Chen C-H, Ho HO, Chen H-H, Sheu M-T (2007) Simultaneous analysis of dextromethorphan and its three metabolites in human plasma using an improved HPLC method with fluorometric detection. J Chromatogr B 859:141–146. https://doi.org/10.1016/j.jchromb.2007.09.017CrossRef

12.

Afshar M, Rouini M-R, Amini M (2004) Simple chromatography method for simultaneous determination of dextromethorphan and its main metabolites in human plasma with fluorimetric detection. J Chromatogr B 802:317–322. https://doi.org/10.1016/j.jchromb.2003.12.009CrossRef

13.

Kim SC, Chung H, Lee SK, Pank YH, Yoo YC, Yun Y-P (2006) Simultaneous analysis of d-3-methoxy-17-methylmorphinan and l-3-methoxy-17-methylmorphinan by high pressure liquid chromatography equipped with PDA. Forensic Sci Int 161:185–188. https://doi.org/10.1016/j.forsciint.2006.05.045CrossRefPubMed

14.

Lurie IS, Cox KA (2005) Rapid chiral separation of dextro- and levo- methorphan using capillary electrophoresis with dynamically coated capillaries. Microgram 53:138–141. https://www.erowid.org/literary/periodicals/microgram/microgram_journal_2005-2.pdf. Accessed Feb 2005

15.

Spanakis M, Vizirianakis IS, Mironidou-Tzouveleki M, Niopas I (2010) A validated SIM GC/MS method for the simultaneous determination of dextromethorphan and its metabolites dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan in biological matrices and its application to in vitro CYP2D6 and CYP3A4 inhibition study. Biomed Chromatogr 23:1131–1137. https://doi.org/10.1002/bmc.1234CrossRef

16.

Rodrigues WC, Wang G, Moore C, Agrawal A, Vincent MJ, Soares JR (2008) Development and validation of ELISA and GC–MS procedures for the quantification of dextromethorphan and its main metabolite dextrorphan in urine and oral fluid. J Anal Toxicol 3:220–226. https://doi.org/10.1093/jat/32.3.220 (open access article)CrossRef

17.

Eichhold TH, Mccauley-Myers DL, Khambe DA, Thompson GA, Hoke SH II (2007) Simultaneous determination of dextromethorphan, dextrorphan, and guaifenesin in human plasma using semi-automated liquid/liquid extraction and gradient liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal 43:586–600. https://doi.org/10.1016/j.jpba.2006.07.018CrossRefPubMed

18.

Kuhlenbeck DL, Eichold TH, Hoke SH II, Baker TR, Mensen R, Wehmeyer KR (2005) On-line solid phase extraction using the Prospekt-2 coupled with a liquid chromatography/tandem mass spectrometer for the determination of dextromethorphan, dextrorphan and guaifenesin in human plasma. Eur J Mass Spectrom 11:199–208. https://doi.org/10.1255/ejms.737CrossRef

19.

Kikura-Hanajiri R, Kawamura M, Miyajima A, Sunouchi M, Goda Y (2011) Chiral analyses of dextromethorphan/levomethorphan and their metabolites in rat and human samples using LC–MS/MS. Anal Bioanal Chem 400:165–174. https://doi.org/10.1007/s00216-011-4707-yCrossRefPubMed

20.

Armstrong DW, Tang Y, Chen S, Zhou Y, Bagwiee C, Chen J-R (1994) Macrocyclic antibiotics as a new class of chiral selectors for liquid chromatography. Anal Chem 66:1473–1484. https://doi.org/10.1021/ac00081a019CrossRef

21.

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.2014.11.009CrossRefPubMed

22.

Hegstad S, Havnen H, Helland A, Spigset O, Frost J (2018) Enantiomeric separation and quantification of R/S-amphetamine in urine by ultra-high performance supercritical fluid chromatography tandem mass spectrometry. J Chromatogr B 1077–1078:7–12. https://doi.org/10.1016/j.jchromb.2018.01.028CrossRef

23.

Hädener M, Bruni PS, Weinmann W, Frübis M, König 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 409:1291–1300. https://doi.org/10.1007/s00216-016-0056-1CrossRefPubMed

24.

Chen L, Yu Y, Wang Y, Xiang P, Duan G (2019) Simultaneous determination of selegiline, desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine in oral fluid by LC/MS/MS. Forensic Toxicol 37:121–131. https://doi.org/10.1007/s11419-018-0443-8CrossRef

25.

Chen L, Yu Y, Duan G, Wang X, Shen B, Xiang P (2019) Simultaneous determination of selegiline, desmethylselegiline, R/S-methamphetamine, and R/S-amphetamine on dried urine spots by LC/MS/MS: application to a pharmacokinetic study in urine. Front Chem 7:248. https://doi.org/10.3389/fchem.2019.00248 (open access article)CrossRefPubMedPubMedCentral

26.

Nishida K, Itoh S, Inoue N, Kudok IN (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 30:232–237. https://doi.org/10.1093/jat/30.4.232 (open access article)CrossRefPubMed

27.

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 877:3226–3230. https://doi.org/10.1016/j.jchromb.2009.07.009CrossRef

28.

Zhao J, Golozoubova V, Cannon B, Nedergaard J (2001) Arotinolol is a weak partial agonist on β₃-adrenergic receptors in brown adipocytes. Can J Physiol Pharmacol 79:585–593. https://doi.org/10.1139/y01-027CrossRefPubMed

29.

Vincenti M, Salomone A, Gerace E, Pirro V (2013) Role of LC–MS/MS in hair testing for the determination of common drugs of abuse and other psychoactive drugs. Bioanalysis 5:1919–1938. https://doi.org/10.4155/bio.13.132CrossRefPubMed

30.

Hui Y, Ping X, Min SH (2021) Current status of hair analysis in forensic toxicology in China. Forensic Sci Res 6:240–249. https://doi.org/10.1080/20961790.2021.1921945CrossRef

31.

Peters FT, Wissenbach DK, Busardò FP, Marchei E, Pichini S (2017) Method development in forensic toxicology. Curr Pharm Des 23:5455–5467. https://doi.org/10.2174/1381612823666170622113331CrossRefPubMed

32.

Wille SMR, Coucke W, Baere TD, Peters FT (2017) Update of standard practices for new method validation in forensic toxicology. Curr Pharm Des 23:5442–5454. https://doi.org/10.2174/1381612823666170714154444CrossRefPubMed

33.

Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC–MS/MS. Anal Chem 75:3019–3030. https://doi.org/10.1021/ac020361sCrossRefPubMed

34.

Nielsen MKK, Johansen SS, Dalsgaard PW, Linnet K (2010) Simultaneous screening and quantification of 52 common pharmaceuticals and drugs of abuse in hair using UPLC–TOF–MS. Forensic Sci Int 196:85–92. https://doi.org/10.1016/j.forsciint.2009.12.027CrossRefPubMed

35.

Scientific Working Group for Forensic Toxicology (2013) Scientific Working Group for Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. J Anal Toxicol 37:452–474. https://doi.org/10.1093/jat/bkt054 (open access article)CrossRef

36.

Avirett A (2008) Solid phase extraction and high performance liquid chromatography determination of dextromehtorphan in hair after exposure to cosmetic treatment. University of North Carolina at Pembroke. https://libres.uncg.edu/ir/uncp/f/Amy_Arirett_Honours_Thesis.pdf. Accessed 3 May 2008

37.

Wei Z, Futian H, Ping G (2010) Simultaneous determination of tolbutamide, omeprazole, midazolam and dextromethorphan in human plasma by LC–MS/MS—a high throughput approach to evaluate drug-drug interactions. J Chromatogr B 878:1169–1177. https://doi.org/10.1016/j.jchromb.2010.03.026CrossRef

38.

Ilisz I, Aranyi A, Pataj Z, Peter A (2013) Enantioseparations by highperformance liquid chromatography using macrocyclic glycopeptide-based chiral stationary phases: an overview. Methods Mol Biol 970:137–163. https://doi.org/10.1007/978-1-62703-263-6_8CrossRefPubMed

39.

Pirkle WH, Finn JM, Hamper BC, Schreiner J, Pribish JR (1982) A useful and conveniently accessible chiral stationary phase for the liquidchromatographic separation of enantiomers. ACS Symp Ser 185:245–260. https://doi.org/10.1021/bk-1982-0185.ch018CrossRef

40.

National Medical Products Administration (2013) Catalogue of narcotic drugs and psychotropic drugs. National Medical Products Administration. https://www.nmpa.gov.cn/directory/web/nmpa/xxgk/fgwj/gzwj/gzwjyp/20131111120001419.html. Accessed 7 Jun 2021 (in Chinese)

41.

Ramachander G, Williams FD, Emele JF (1977) Determination of dextrorphan in plasma and evaluation of bioavailability of dextromethorphan hydrobromide in humans. J Pharm Sci 66:1047–1048. https://doi.org/10.1002/jps.2600660740 (open access article)CrossRefPubMed

42.

Wolfe TR, Caravati EM (1995) Massive dextromethorphan ingestion and abuse. Am J Emerg Med 13:174–176. https://doi.org/10.1016/0735-6757(95)90088-8CrossRefPubMed

43.

Ginski MJ, Witkin JM (1994) Sensitive and rapid behavioral differentiation of N-methyl-{d}-aspartate receptor antagonists. Psychopharmacology 114:573–582. https://doi.org/10.1007/BF02244987CrossRefPubMed

44.

Bobo WV, Fulton RB (2004) Commentary on: severe manifestations of coricidin intoxication. Am J Emerg Med 22:624–625. https://doi.org/10.1016/j.ajem.2004.09.011CrossRefPubMed

45.

Bryner JK, Wang UK, Hui JW, Bedodo M, MacDougall C, Anderson IB (2006) Dextromethorphan abuse in adolescence : an increasing trend: 1999–2004. Arch Pediatr Adolesc Med 160:1217–1222. https://doi.org/10.1001/archpedi.160.12.1217CrossRefPubMedPubMedCentral

46.

Jain R, Chatterjee B, Gupta A (2021) Assessment of codeine abuse among substance-abuse patients based on urinalysis: a retrospective study. Asian J Psychiatr 62:1–2. https://doi.org/10.1016/j.ajp.2021.102719CrossRef

Titel: Chiral analysis of dextromethorphan and levomethorphan in human hair by liquid chromatography–tandem mass spectrometry
verfasst von: Jiao-jiao Ji
Junbo Zhao
Ping Xiang
Hui Yan
Min Shen
Publikationsdatum: 28.03.2022
Verlag: Springer Nature Singapore
Erschienen in: Forensic Toxicology / Ausgabe 2/2022
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-022-00620-2

Neu im Fachgebiet Rechtsmedizin

Open Access 15.04.2024 | Biomarker | Schwerpunkt: Next Generation Pathology

Springer Medizin

Chiral analysis of dextromethorphan and levomethorphan in human hair by liquid chromatography–tandem mass spectrometry

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2022

Comparison between human liver microsomes and the fungus Cunninghamella elegans for biotransformation of the synthetic cannabinoid JWH-424 having a bromo-naphthyl moiety analysed by high-resolution mass spectrometry

Determination of cyanide in blood by GC–MS using a new high selectivity derivatization reagent 1,2,3,3-tetramethyl-3H-indolium iodide

Long-term stability of 24 synthetic cannabinoid metabolites spiked into whole blood and urine for up to 168 days, and the comparable study for the 6 metabolites in non-spiked real case specimens stored for 1–5 years

Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine

Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography–tandem mass spectrometry

Two DFSA cases involving midazolam clarified by the micro-segmental hair analyses

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie