Determination of tiapamil and of its two main metabolites in plasma and in urine by high-performance liquid chromatography

Abstract

Selective high-performance liquid chromatographic methods for the determination of tiapamil and its two main metabolites in plasma and urine are described. Tiapamil together with its metabolites is extracted at alkaline pH into dichloromethane. Separation is carried out using normal-phase high-performance liquid chromatography with ultraviolet detection (278 nm). The unchanged drug and the desmethyl metabolite are analysed simultaneously. The second metabolite is analysed separately under more polar conditions. The sensitivity limits are 50 ng/ml for tiapamil, 100 ng/ml for the desmethyl metabolite and 75 ng/ml for the second metabolite, using 0.5 ml of plasma. The sensitivity limits in urine are 100 ng/ml for all three compounds using a 0.5 ml specimen. The method has been applied to the analysis of human plasma and urine after intravenous (70 mg) and oral (400 mg) administration of tiapamil.