Analysis of time-lapse changes of d- and l-enantiomers of racemic ethylamphetamine and stereoselective metabolism in rat urine by HPLC determination.

Abstract

The analysis of time-lapse changes of d- and l-enantiomers after administration of racemic dl-ethylamphetamine (EAMP) to rats was performed by a high-performance liquid chromatograph equipped with a chiral activity column. After oral administration of dl-EAMP to five rats (dose, 15 mg/kg), the rat urine specimens were collected at four time intervals, 0-4, 4-12, 12-20, and 20-24 h. The two enantiomers of nonmetabolized EAMP and the two enantiomers of metabolized amphetamine (AMP) in urine were simultaneously detected within 20 min. The rate of urinary excretion during 24 h was 3.67% for d-EAMP, 1.03% for l-EAMP, 2.14% for d-AMP, and 1.92% for l-AMP. The total percent of the excreted doses of EAMP and AMP was approximately 8.8% of the administered dosage of dl-EAMP (5.81% for the d-enantiomers and 2.95% for the l-enantiomers). The l/d ratio was 0.51, which was significantly smaller than that (1.01) of the original dl-EAMP powder used (p < .01). The percentages of the doses of l-EAMP in each collection time were significantly less than those of d-EAMP (p < .01), and the l/d ratios of nonmetabolized EAMP decreased to 0.17 within 24 h. For the AMP metabolites, there was a somewhat greater percentage of l-AMP in urine collected up to 4 h than d-AMP (p < .05). Thereafter, it decreased more slowly than d-AMP with time. The l/d ratios of AMP changed from 1.57 to 0.76 within 24 h. The greater decrease of l-EAMP as compared with d-EAMP suggested the stereoselective metabolism of dl-EAMP in rats.