The use of solid probe chemical ionization mass spectrometry and gas chromatography-chemical ionization mass spectrometry in quantitation of drugs in biological fluids. Determination of tolbutamide and its metabolites in human plasma.

Abstract

Quantitative methods based on chemical ionization mass spectrometry are described for the determination of tolbutamide, a sulfonylurea, and its metabolites from human plasma. The sulfonylureas are extracted from the acidified plasma and then N-1 methylated with diazomethane. The methylated compounds can be subjected to gas chromatography where they are partially cleaved to the corresponding N-1 methylated sulfonamides. Alternatively, the methylated compounds can be introduced into the ion source by means of a solid sampler. The sulfonylureas upon evaporation from the solid sampler or the formed sulfonamide and the parent sulfonylurea upon elution from the gas chromatographic column are subjected to chemical ionization with methane as the reactant gas. The [M + H]+ ions formed are measured quantitatively with respect to the deuterium substituted internal standards. It is suggested that the technique of introducing biological extracts into the ion source via a solid probe may be applied for the quantification of compounds that are unstable under gas-liquid chromatographic conditions. Both the gas chromatographic and the non gas chromatographic methods provided excellent and comparable results. The plasma level-time profile of tolbutamide and its metabolites in a diabetic patient following the administration of 1.0 g tolbutamide intravenously is presented.