Formation of Thermally Stable Derivatives for Determination of Tolbutmide and Chlorpropmide by Gas Chromatography

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Abstract
We have developed a rapid, sensitive and specific method for the quantitation of serum levels of two antidiabetic sulfonylureas, chlorpropamide (I) and tolbutamide (II). Thermally stable derivatives of I, II and the major products of metabolism of 11, hydroxytolbutamide and carboxytolbutamide, were prepared. Serum levels of I and II were determined following extraction of acidified serum with ethyl acetate, formation of N-methyl derivatives with diazomethane, and then formation of the N-methyl-N′-tri-fluoroacetyl derivatives with trifluoroacetic anhydride. The derivatized compounds were analyzed by gas chromatography/mass spectrometry, and by GLC using flame ionization detection, and quantitated using the internal standard method.