Stereoselective analyses of selegiline metabolites: possible urinary markers for selegiline therapy
by
Hasegawa M, Matsubara K, Fukushima S,
Maseda C, Uezono T, Kimura K
Department of Legal Medicine,
Shimane Medical University, Izumo, Japan.
Forensic Sci Int 1999 Apr 26; 101(2):95-106


ABSTRACT

The stereoselective analysis of selegiline metabolites in human urine and plasma by gas chromatography using the chiral column with the non-chiral reagent was investigated for the differentiation of selegiline therapy from the methamphetamine (MA) abuse. This method gave clear separations of MA and amphetamine (AM) isomers without any artifactual optical-opposite peaks due to the reagent. After the administration of selegiline tablets, desmethylselegiline (DMS), MA and AM were observed as (-)-isomers in the urine and plasma. Within the first 48 h after dosing, approximately 40% of selegiline administered was excreted in urine as these three metabolites. The parent drug, selegiline, was not detected in any urine or plasma samples. On the other hand, MA and AM were observed only as (+)-isomers in the urine of MA abusers. For the distinction of selegiline users from street MA abusers in urinalysis, (-)-DMS, a specific metabolite of selegiline, was not a suitable marker. (-)-DMS rapidly disappeared from urine and was excreted only 1% of the given dose. By the moment analysis with the trapezoidal integration, the mean residence times of (-)-DMS in plasma and urine were 2.7 and 3.8 h, respectively, which were 5-20 times shorter than those of (-)-MA or (-)-AM. The values of AM/MA in the urine increased from 0.24 to 0.67 (r = 0.857) along with time after the selegiline administration. This ratio was not a sufficient marker to differentiate selegiline users from MA abusers, although the values of AM/MA in 74% of MA abusers were less than 0.24. The present GC technique improved the chiral analyses of MA and AM. This chiral analysis is the most useful technique to avoid the misinterpretation in the discrimination between clinical selegiline therapy and illicit MA use.
Review
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Interactions
Cytochrome P450
Alzheimer's disease
Methamphetamine test
Selegiline and the brain
Selegiline and nitric oxide
Selegiline / neuroprotection
Selegiline and life-expectancy
Selegiline for longer-lived flies
Selegiline: product information
Selegiline as an immunostimulant
Selegiline for cocaine dependence


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