Sensitive method for determination of captopril in biological fluids by gas chromatography-mass spectrometry

A sensitive method for the determination of captopril in blood and urine by gas chromatography-mass spectrometry is described. In order to prevent oxidative degradation of captopril, its sulph-hydryl group was immediately protected by treatment with N-ethylmaleimide (NEM), and the resulting NEM adduct was then converted into the bis(pentafluorobenzyl) derivative. Derivatized captopril was separated on a 2% OV-1 column, exhibiting a single peak of the correct theoretical shape. The detection limit was estimated to be 100 pg by using S-benzylcaptopril as an internal standard. The blood level and urinary excretion of unchanged captopril orally administered to dogs were determined by the proposed method. In addition, epimerization of the proline moiety and formation of the sulphoxide or sulphone through the esterification step are also described.