Investigations into the chirality of the metabolic sulfoxidation of cimetidine

Abstract

AbstractThe individual enantiomers of cimetidine sulfoxide were resolved by preparative chromatography using a Chiralcel OC stationary phase and were characterized by the determination of optical rotation and circular dichroism spectra. Cimetidine sulfoxide was isolated from the urine of two healthy male volunteers following oral administration of cimetidine (400 mg). Urine was collected every 2 h for 12 h postdosing, after which time HPLC analysis indicated negligible recovery of the drug as the sulfoxide. Some 7% of the dose was recovered as cimetidine sulfoxide over this period. The enantiomeric composition of cimetidine sulfoxide was determined by sequential achiral—chiral chromatography using the OC phase. Over the collection period the enantiomeric ratio was found to be constant in all samples at (+/−) of 71 ± 2.5:29 ± 2.5. The enantiomeric composition of cimetidine sulfoxide was also determined in rat urine (24 h) following the administration of cimetidine (30 mg/kg po) to male Wistar rats (n = 7). The enantiomeric ratio in this case was found to be (+/−) 57 ± 2.3:43 ± 2.3. These preliminary data indicate that sulfoxidation of cimetidine is stereoselective with respect to the (+)‐enantiomer and that species variation in enantiomeric composition occurs. © 1994 Wiley‐Liss, Inc.