Radioimmunoassay for imidapril, a new angiotensin-converting enzyme inhibitor, and imidaprilat, its active metabolite, in human plasma and urine.

A radioimmunoassay (RIA) was investigated for the determination of imidapril and its active metabolite, imidaprilat, in human plasma and urine. Imidapril is a new angiotensin-converting enzyme inhibitor and an oral prodrug of imidaprilat. Imidapril was determined after conversion to imidaprilat with esterase. Antiserum was raised in rabbits against the p-amino derivative of imidaprilat conjugated to bovine serum albumin. Radioligand was prepared by iodination (125I) of the p-hydroxybenzoylamino derivative of imidaprilat. Cross-reactivities of anti-imidaprilat antiserum for imidapril, its metabolites and several cardiovascular drugs were low. The calibration range was 0.1-100 ng ml-1 using a 100 microliters of human plasma of urine. Intra- and inter-day variations of imidaprilat assay in plasma were 2.0-7.9 and 4.1-6.2%, respectively, and intra- and inter-day variations of imidapril assay in plasma were 5.4-10.7 and 7.9-18.1%, respectively. The variations of the assay in urine were a little smaller than those in plasma. The recovery of imidaprilat and imidapril spiked in plasma or urine samples was approximately 100%. A good correlation between RIA and high-performance liquid chromatograpy was observed for both plasma and urine samples. Furthermore, this method was applied to the determination of imidaprilat and imidapril in human plasma and urine samples, for the evaluation of the pharmacokinetics of imidapril in humans. From the results, it was demonstrated that the developed RIA was useful for the determination of imidaprilat and imidapril in human plasma and urine, and was applicable to pharmacokinetic studies in humans.