Measurement of antidiabetic sulfonylureas in serum by gas chromatography with electron-capture detection.

A method is described for measurement of chlorpropamide, tolbutamide, and the tolbutamide metabolites hydroxymethyltolbutamide and carbotytolbutamide in blood. It consists of formation of the thermally stable methyl-trifluoroacetyl derivatives of chlorpropamide and tolbutamide, and the methyl-heptafluorobutyryl derivatives of hydroxymethyltolbutamide and carboxytolbutamide, which are then analyzed by electron-capture gas chromatography. Measurements of blood levels of the compounds with this method have been verified by quantitation of the same samples using gas chromatography-mass spectrometry in the mass fragmentography mode. Blood level values and beta-phase half-time disappearance rates of chlorpropamide, tolbutamide, hydroxymethyltolbutamide, and carboxytolbutamide were measured in normal volunteers following an oral dose of chlorpropamide or tolbutamide. Blood levels of the four compounds were also determined in a few diabetics receiving continuous daily treatment.