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

Abstract

1. The metabolism of [₃H]-5-(—)-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 metabolities 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 (> 95%) and very little cotinine was detected (< 1 %) in the urine.

3. Two unidentified metabolites of [³H]-5-(—)-cotinine were detected which collectively constituted approximately 20% of total urinary tritium.