Stereochemical Analysis of Methorphan Using (−)‐Menthyl Chloroformate

Abstract

Forensic laboratories around the world have seen an increase in the number of drug seizures containing methorphan. Levomethorphan is a narcotic and a controlled substance, and its enantiomer dextromethorphan is an antitussive agent used in over-the-counter medications. For the forensic analysis of seized drugs containing methorphan, it is important to report the stereochemical composition of the drug. Ideally, a method based on common forensic laboratory instrumentation is desirable. The use of the chiral derivatizing agent (-)-menthyl chloroformate followed by routine gas chromatography-mass spectrometry analysis of the derivative was shown to successfully determine the stereochemical composition of methorphan. This approach was applied to a street seizure containing methorphan proving that it was pure dextromethorphan. The derivatives of dextro- and levomethorphan were subjected to mass spectroscopic and nuclear magnetic resonance analysis, which confirmed that the structure of the derivatives remained unchanged as a result of the derivatization process.

Dextromethorphan/levomethorphan issues in a case of opiate overdose

“…[7,8,19,20] Using our method, a complete separation of pholcodine (I.S.) [7,8,19,20] Using our method, a complete separation of pholcodine (I.S.)…”

“…Indeed, there are hundreds of cough and cold preparations containing d-methorphan alone or in combination with analgesic (acetaminophen, acetyl salicylic acid), decongestant (phenylephrine, pseudoephedrine), anthistaminic (chlorpheniramine, brompheniramine, pheniramine), and/or expectorant mucolytic agents. [7][8][9][10] Both notifications and scientific papers often report methorphan as an adulterant, since the analytical methods used for heroin analysis cannot distinguish between the two stereoisomers. This action is responsible for the hallucinogenic and dissociative effects experienced by the subjects who abuse d-methorphan.…”

“…[6] Moreover, the use of methorphan as adulterant is reported in recent scientific literature. [7][8][9][10] Both notifications and scientific papers often report methorphan as an adulterant, since the analytical methods used for heroin analysis cannot distinguish between the two stereoisomers. On the other hand, some papers report the identification of dextromethorphan because the gas chromatography-mass spectrometry (GC-MS) spectra of both stereoisomers are recognized by the library as d-methorphan.…”

Chiral analysis of methorphan in opiate-overdose related deaths by using capillary electrophoresis

“…Moreover, the other chiral methods reported in the literature for methorphan analysis, based on the use of HPLC-DAD, HPLC-MS, and GC-MS, were not applied to the analysis of cadaveric blood [12][13][14][15].…”

“…The traditional methods applied to the analysis of chiral compounds are typically based on GC and HPLC, through the formation of diastereoisomers or using chiral columns [14][15][16].…”