Biotransformation of primary nicotine metabolites. II. Metabolism of [3H]-S-(-)-cotinine in the guinea pig: determination of in vivo urinary metabolites by high-performance liquid-radiochromatography.

1. The metabolism of [3H]-S-(-)-cotinine in vivo has been investigated in the guinea pig. The quantitive determination of urinary metabolites has been carried out using a high-performance liquid radiochromagraphic procedure. Metabolite analysis of C- and N-oxidation products, and N-methylcotininium ion, were carried out on two chromatographic systems: (a) Partisil-10 SCX cation-exchange chromatography, and (b) Partisil-10 ODS reverse-phase chromatography. 2. 3-Hydroxycotinine was the major urinary metabolite of cotinine in the guinea pig, accounting for 57% of the total radioactivity in the urine. Cotinine-N-oxide constituted 18% of total metabolites in the urine, whereas neither nicotine nor the N-methylcotininium ion were detected as urinary metabolites of [3H]-S-(-)cotinine. S-(-)-Cotinine was extensively metabolized in the guinea pig; total recovery of radioactivity in 24 h urine was very high (greater than 95%) and very little cotinine was detected (less than 1%) in the urine. 3. Two unidentified metabolites of [3H]-S-(-)-cotinine were detected which collectively constituted approximately 20% of total urinary tritium.