GLC determination of plasma levels of intact chlorpropamide or tolbutamide.

A GLC procedure was developed for the quantitative estimation of intact chlorpropamide and tolbutamide concentrations in plasma; the drugs are used as mutual internal standards. After extraction of plasma containing the drug and internal standard with toluene, the dried residue is treated with ethereal diazomethane to form the methyl derivatives of tolbutamide and chlorpropamide. Aliquots of the ethereal solution are injected into a gas chromatograph equipped with a glass-lined injection port and glass column packed with a phenyl methyl silicone fluid (OV-25) on Chromosorb W, which facilitates the intact determination of the methyl derivatives of the drugs. The response to the flame-ionization detector was linear over a range of 0.20-25 mug/ml, with a 0.05-mug/ml limit of detectability for both drugs. The method compares favorably with a recently developed high-pressure liquid chromatographic procedure and is adequate for following blood level profiles of single doses of chlorpropamide (125 mg) and tolbutamide (250 mg). Mass spectral evidence showing that intact sulfonylureas are measured is presented.