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Published in: Forensic Toxicology 2/2022

28-03-2022 | Dextromethorphan | Original Article

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

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

Published in: Forensic Toxicology | Issue 2/2022

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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.
Literature
6.
go back to reference 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 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/​1556365070160644​3 (open access article)CrossRef
15.
go back to reference 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 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.
go back to reference 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 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
18.
go back to reference 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 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
26.
go back to reference 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 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
Metadata
Title
Chiral analysis of dextromethorphan and levomethorphan in human hair by liquid chromatography–tandem mass spectrometry
Authors
Jiao-jiao Ji
Junbo Zhao
Ping Xiang
Hui Yan
Min Shen
Publication date
28-03-2022
Publisher
Springer Nature Singapore
Published in
Forensic Toxicology / Issue 2/2022
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-022-00620-2

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