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.     

The Effects of Dextromethorphan on Driving Performance and the Standardized Field Sobriety Test

Dextromethorphan (DXM) is abused most commonly among adolescents as a recreational drug to generate a dissociative experience. The objective of the study was to assess driving with and without DXM ingestion. The effects of one‐time maximum daily doses of DXM 120 mg versus a guaifenesin 400 mg dose were compared among 40 healthy subjects using a crossover design. Subjects’ ability to drive was assessed by their performance in a driving simulator (STISIM^® Drive driving simulator software) and by conducting a standardized field sobriety test (SFST) administered 1‐h postdrug administration. The one‐time dose of DXM 120 mg did not demonstrate driving impairment on the STISIM^® Drive driving simulator or increase SFST failures compared to guaifenesin 400 mg. Doses greater than the currently recommended maximum daily dose of 120 mg are necessary to perturb driving behavior.     

Dextromethorphan abuse leading to assault, suicide, or homicide

Abstract: Dextromethorphan is a commonly encountered antitussive medication which has found additional therapeutic use in the treatment of pseudobulbar disorder and as an adjunct to opiate use in pain management. Dextromethorphan at high doses has phencyclidine‐like effects on the NMDA receptor system; recreational use of high doses has been found to cause mania and hallucinations. The toxicology and pharmacology of the drug in abuse are reviewed, and the historical literature of adverse psychiatric outcomes is assessed. Five new cases of dextromethorphan intoxication that resulted in assault, suicide, and homicide are reported, together with the corresponding toxicology results. Blood concentrations ranged from 300 to 19,000 μg/L. These results are compared with typical concentrations reported in therapeutic use and impaired driving cases. Based on these findings, dextromethorphan should be considered as a potential causative agent in subjects presenting with mania, psychosis, or hallucinations, and abusers are at risk for violent and self‐destructive acts.