RADIOIMMUNOASSAY OF A NEW ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR (PERINDOPRIL) IN HUMAN PLASMA AND URINE - ADVANTAGES OF COUPLING ANION-EXCHANGE COLUMN CHROMATOGRAPHY WITH RADIOIMMUNOASSAY

被引：28

作者：

DOUCET, L ^{[1
]}

DEVEYRAC, B ^{[1
]}

DELAAGE, M ^{[1
]}

CAILLA, H ^{[1
]}

BERNHEIM, C ^{[1
]}

DEVISSAGUET, M ^{[1
]}

机构：

[1] INST RECH INT SERVIER,F-92200 NEUILLY SUR SEINE,FRANCE

来源：

JOURNAL OF PHARMACEUTICAL SCIENCES | 1990年 / 79卷 / 08期

关键词：

D O I：

10.1002/jps.2600790817

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 (125I) 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 immuno‐reactive 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. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company

引用

页码：741 / 745

页数：5

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