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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 24,
Number 4, May/June 2000, pp. 238-244
Determination
of Enantiomeric Metabolites of l-Deprenyl, d-Methamphetamine, and
Racemic Methamphetamine in Urine by Capillary Electrophoresis: Comparison of Deprenyl
Use and Methamphetamine Use 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-b-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.Eun-Mi
Kim1,3, Hee-Sun Chung3, Kong-Joo Lee1,2, and Hwa-Jung Kim1,2,*
1Research Institute of Pharmaceutical Sciences, College of Pharmacy and 2Center
for Cell Signaling Research, Ewha Womens University, Seoul 120-750, South Korea
and 3National Institute of Scientific Investigation, Seoul 158-097, South Korea Reproduction
of editorial content of this journal is prohibited without publishers
permission.
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