Stereoisomeric Identification of Norephedrine Derived from Methamphetamine or Amphetamine: Urinalysis Results of 33 Methamphetamine Abusers and 1 Amphetamine Abuser in Japan

Abstract

Stereoisomeric identification of norephedrine (NE) derived from methamphetamine (MA) or amphetamine (AM) was investigated by SIM-GC/MS assay using the urine of 33 MA abusers and 1 AM abuser. The assay simultaneously identified TFA-derivatized MA and AM metabolites, including AM, p-hydroxyl-MA (p-HMA), and p-hydroxyl-AM (p-HAM). The analysis lasted approximately 43 min, with a signal-to-noise ratio of >or=3 and a detection limit of 50 ng/mL. Among 12 urine samples from different subjects, only the S (+) form of MA and its metabolites (AM, p-HMA, p-HAM) was detected, however, a (1R,2S)-(-)-NE stereoisomer was also identified. Among the urine samples of two subjects, only the R (-) form of MA and its metabolites (AM, p-HMA, p-HAM) was detected, while NE was not detected. Following urinalysis of urine obtained from 19 MA abusers and 1 AM abuser, only the (1R,2S)-(-)-NE stereoisomer was identified, while unmetabolized MA, AM, and their metabolites (p-HMA, p-HAM), showed stereoselective metabolism. Although (1R,2S)-(-)-ephedrine (EP) alone was found in the urine of 1 (S)-(+)-MA user and 1 (S)-(+)- and (R)-(-)-MA user among 33 MA users, it was not present in the urine of the remaining 31 subjects. Therefore, (1R,2S)-(-)-NE was likely not of (1R,2S)-(-)-EP origin and was most likely from (S)-(+)-AM of the MA metabolite. The production ratio of (1R,2S)-(-)-NE to (S)-(+)-AM ranged from 0.01 to 0.25 in MA abusers and was 0.12 in AM abusers.