ASSAY OF SULFONYLUREAS IN HUMAN-PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

The 2 oral hypoglycemic drugs tolbutamide and chlorpropamide are widely used in the management of certain types of maturity-onset diabetes. A sensitive and specific high-performance liquid chromatographic procedure is described for the determination of these drugs in [human] plasma in the presence of their metabolites is described. The ether extract of acidified plasma is redissolved in the mobile phase, 17% acetonitrile in 0.05 M aqueous ammonium formate, and chromatographed on a reverse-phase column on a high-performance liquid chromatograph fitted with a UV absorbance detector. Quantitation of plasma samples containing less than 0.5 .mu.g/ml of chlorpropamide and 5 .mu.g/ml of tolbutamide is reported, using these drugs as mutual internal standards. The retention times of the metabolites are such that they do not interfere in the procedure. The assay method was tested in a human volunteer with both drugs and found suitable for single-dose pharmacokinetic studies.