QUANTITATIVE-DETERMINATION OF THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR CILAZAPRIL AND ITS ACTIVE METABOLITE CILAZAPRILAT IN PHARMACEUTICALS AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH AMPEROMETRIC DETECTION

A rapid and simple high-performance liquid chromatographic method with amperometric detection has been developed for the quantitation of cil azapril and its active metabolite and degradation product cilazaprilat in urine and tablets. The chromatographic system consisted of a mu Bo ndapak C-18 column, using a mixture of methanol-5 mM phosphoric acid ( 50:50, v/v) as mobile phase, which was pumped at a flow-rate of 1.0 ml /min. The column was kept at a constant temperature of (40 +/- 0.2)deg rees C. Detection was performed using a glassy carbon electrode at a p otential of 1350 mV. Sample preparation for urine consisted of a solid -phase extraction using C-8 cartridges. This procedure allowed recover ies greater than 85% for both compounds. The method proved to be accur ate, precise and sensitive enough to be applied to pharmacokinetic stu dies and it has been applied to urine samples obtained from four hyper tensive patients (detection limit of 50 ng/ml for cilazapril and 40 ng /ml for cilazaprilat in urine). Results were in good agreement with ph armacokinetic data. (C) 1998 Elsevier Science B.V. All rights reserved .