Determination of enantiomeric metabolites of l-deprenyl, d- methamphetamine, and racemic methamphetamine in urine by capillary electrophoresis: Comparison of deprenyl use and methamphetamine use

Abstract

The enantiomeric analysis of urine collected from rats administered l- deprenyl, d-methamphetamine (MA), or dl-MA and from healthy male volunteers who ingested l-deprenyl by capillary electrophoresis (CE) using carboxy methylated-β-cyclodextrin (CMCD) as a chiral selector was investigated to compare the metabolic pattern of l-deprenyl with the metabolism of d- or dl- MA. Urine from illegal drug abusers was also analyzed for the comparison of therapeutic drug (l-deprenyl) use with illicit drug (d-MA) use. MA enantiomers (l-, d-), amphetamine (AM) enantiomers (l-, d-), l-deprenyl, and desmethylselegiline (DMS) enantiomers (l-, d-) were simultaneously separated and detected with clear resolution. l-Deprenyl and its metabolites, l-MA, l- AM, and l-DMS, were detected in rat urine sample collected up to 24 h after oral administration of l-deprenyl (10 mg/kg), and the urinary l-AM/l-MA ratio was 2.45 ± 0.55. This AM/MA ratio was significantly higher than the ratios obtained from rats administered with d-MA (5 mg/kg) and dl-MA (10 mg/kg). The d-AM/d-MA ratio was 0.98 ± 0.25 for the d-MA treatment, and the d-AM/d-MA and l-AM/l-MA ratios were 0.72 ± 0.24 and 0.71 ± 0.21, respectively, for the dl-MA treatment. Analysis of human urine revealed that, unlike in rat urine, the MA content was much greater than the AM content, resulting in the AM/MA ratios being far lower in cases of healthy adult men treated with l- deprenyl (10 mg) and MA abusers. The AM/MA ratio from l-deprenyl users (0.33 ± 0.03) was significantly higher than the ratio from MA abusers (0.20 ± 0.12). Results indicate that although metabolic patterns of the drugs in rat and humans may be different, the AM/MA ratio from l-deprenyl use is significantly higher than the ratio from MA use in both rat and human urine. This ratio, however, cannot give conclusive proof of deprenyl or MA use in humans. The simultaneous chiral separation for all the metabolites of l- deprenyl and MA by CE analysis used in this study could provide rapid and simple discrimination between therapeutic drug use and illegal drug abuse.