A quantitative gas-liquid chromatographic method for the determination of pethidine and its metabolites, norpethidine and pethidine N-oxide in human biological fluids

Abstract

A sensitive and selective analytical method, to measure pethidine and its metabolites norpethidine and pethidine N-oxide simultaneously in human biological fluids is described. The procedure involves preliminary extraction of pethidine and norpethidine from the alkalinised fluid into diethyl ether, followed by concentration and analysis using a gas-liquid chromatograph with a flame ionisation detector. Two alternative gas-liquid chromatographic systems have been used successfully: one involves acylation of norpethidine prior to injection on the column, the other does not require derivative formation and was chosen for routine analysis. Benzphetamine hydrochloride is used as the internal standard for quantitation by the peak area ratio technique. The method will detect as little as 20 ng/ml of pethidine and norpethidine in a 5-ml sample and has been employed to measure pethidine, norpethidine and pethidine N-oxide in human urine, and pethidine and norpethidine in plasma and whole blood after a single intramuscular therapeutic dose.