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High-performance liquid chromatographic analysis of captopril in plasma.

A sensitive assay is described for quantitating plasma captopril levels. Captopril is an orally active inhibitor of angiotensin-converting enzyme. Blood from patients taking this drug was collected into tubes containing edetate and ascorbic acid, and the plasma was separated by centrifugation. After addition of an internal standard, the plasma was deproteinized and the supernate was adjusted to pH 6.5 N-(1-Pyrene)-maleimide was added to derivatize captopril and an internal standard to fluorescent adducts. These derivatives then were extracted into ethyl acetate-benzene (1:1) and separated from other derivatized thiols by high-performance liquid chromatography. The sensitivity of the assay was 150 pmoles/ml. Preliminary pharmacokinetics were obtained in patients taking captopril chronically for essential hypertension. After administration of 100 mg of captopril for patients who had fasted overnight, the plasma levels rose rapidly; peak levels were obtained at approximately 37 min. Thereafter, the plasma levels declined rapidly, and the terminal half-life was approximately 40 min. In these patients, the time course of the plasma levels did not reflect changes in blood pressure, so there appeared to be no direct relationship between plasma levels of the parent compound and blood pressure changes.