Simultaneous HPLC analysis of optical isomers of methamphetamine and its metabolites, and stereoselective metabolism of racemic methamphetamine in rat urine.

Simultaneous identification of optical isomers (D and L) of methamphetamine (MAMP), amphetamine (AMP), para(p)-hydroxy(OH)-MAMP, and para(p)-hydroxy(OH)-AMP in rat urine was attempted by high-performance liquid chromatography (HPLC). They were determined as benzoyl derivatives. After administration of D- or L-isomer (15 mg/kg), only D- or L-isomers of the above mentioned metabolites were found in rat urine. In rats administered racemic MAMP (15 mg/kg), each percent dose of L-isomers of MAMP or AMP excreted at four collection times up to 24 h was less than that of the D-isomer (L/D less than 1.00), but the doses of L-isomers of p-OH-MAMP and p-OH-AMP excreted were higher than those of D-isomers (L/D greater than 1.00). Simultaneous analysis within 36 minutes showed good peak resolution. The L/D ratio for each metabolite decreased with time. The total percent doses of D- or L-isomer excreted by 24 hours were about 50% of the administered dose, 23.70 +/- 1.45% for the D-isomer, 25.70 +/- 1.54% for the L-isomers. The total L/D ratio was 1.08 +/- 0.03. These results indicated that Wistar rats have no chiral isomerization enzyme of MAMP, and show stereoselective metabolism of DL-MAMP. In the optical isomer analysis of 11 MAMP powder samples and 28 human urine specimens obtained from Japanese abusers, only D-MAMP was detected in the powder, and D-MAMP and D-AMP were detected in urine, respectively. This suggested that humans have no chiral isomerization enzyme of D-MAMP.