DETERMINATION OF CAPTOPRIL IN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY FOR PHARMACOKINETIC STUDIES

A high-performance liquid chromatographic method is described for the determination of free captopril in human plasma. N-Acetyl-L-cysteine ( NAG) was used as an internal standard. Plasma samples were immediately derivatized with N-(1-pyrenyl)maleimide (NPM) and stabilized with 11 M HCl. The drug of interest was isolated using a liquid-liquid extract ion with ethyl acetate and separation was obtained using a reversed-ph ase column under isocratic conditions with fluorescence detection. The sample volume was 150 mu l plasma. The intra- and inter-day accuracy and precision, determined as relative error and coefficient of variati on respectively, were less than 10%. The lower limit of quantitation, based on standards with acceptable coefficients of variation, was 25 n g/ml. No endogenous compounds were found to interfere. The linearity w as assessed in the range of 25-600 ng/ml. This method has been demonst rated to be suitable for pharmacokinetic studies in humans.