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

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 ∼43 min, with a
signal-to-noise ratio of ≥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.