Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay
- Immunotech S. A. Case 915, Marseille (France)
Perindopril (P) is a prodrug whose active metabolite perindoprilat (PT) is an antihypertensive agent which acts by inhibition of angiotensin-converting enzyme (ACE). Anti-PT antiserum was produced in a rabbit immunized against PT that was covalently linked to bovine serum albumin. The radioligand is an iodinated ({sup 125}I) derivative of PT-glycyltyrosinamide. Both the drug (PT) and the prodrug (P) are assayed in the same sample; PT is assayed as is and P is assayed after quantitative alkaline hydrolysis into PT. Certain data obtained from such assays suggest the occurrence in plasma and urine of a third immunoreactive component. A chromatographic fractionation of samples allowed us to isolate a new immunoreactive metabolite which was further identified as a glucuronide of PT (PT-G). Therefore, the whole assay was carried out as follows: biological samples were fractionated by stepwise chromatography on a anion-exchange resin (the first fraction contained P, the second contained PT, and the third contained PT-G); and RIA was performed on fractions 2 and 3 as is, and on fraction 1 after alkaline hydrolysis. Performances and assessments of this method are presented together with an example of a pharmacokinetic profile.
- OSTI ID:
- 6172045
- Journal Information:
- Journal of Pharmaceutical Sciences; (USA), Vol. 79:8; ISSN 0022-3549
- Country of Publication:
- United States
- Language:
- English
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550201* - Biochemistry- Tracer Techniques