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Title: Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay

Abstract

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.

Authors:
; ; ; ; ;  [1]
  1. Immunotech S. A. Case 915, Marseille (France)
Publication Date:
OSTI Identifier:
6172045
Resource Type:
Journal Article
Journal Name:
Journal of Pharmaceutical Sciences; (USA)
Additional Journal Information:
Journal Volume: 79:8; Journal ID: ISSN 0022-3549
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ENZYME INHIBITORS; RADIOIMMUNOASSAY; ALBUMINS; BLOOD PLASMA; CATTLE; IODINE 125; ION EXCHANGE CHROMATOGRAPHY; LIGANDS; MAN; URINE; ANIMALS; BETA DECAY RADIOISOTOPES; BIOASSAY; BIOLOGICAL MATERIALS; BIOLOGICAL WASTES; BLOOD; BODY FLUIDS; CHROMATOGRAPHY; DAYS LIVING RADIOISOTOPES; DIAGNOSTIC TECHNIQUES; DOMESTIC ANIMALS; ELECTRON CAPTURE RADIOISOTOPES; IMMUNOASSAY; IMMUNOLOGY; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; MAMMALS; MATERIALS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PRIMATES; PROTEINS; RADIOASSAY; RADIOIMMUNODETECTION; RADIOIMMUNOLOGY; RADIOISOTOPES; RUMINANTS; SEPARATION PROCESSES; TRACER TECHNIQUES; VERTEBRATES; WASTES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Doucet, L, De Veyrac, B, Delaage, M, Cailla, H, Bernheim, C, and Devissaguet, M. Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay. United States: N. p., 1990. Web. doi:10.1002/jps.2600790817.
Doucet, L, De Veyrac, B, Delaage, M, Cailla, H, Bernheim, C, & Devissaguet, M. Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay. United States. https://doi.org/10.1002/jps.2600790817
Doucet, L, De Veyrac, B, Delaage, M, Cailla, H, Bernheim, C, and Devissaguet, M. 1990. "Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay". United States. https://doi.org/10.1002/jps.2600790817.
@article{osti_6172045,
title = {Radioimmunoassay of a new angiotensin-converting enzyme inhibitor (perindopril) in human plasma and urine: Advantages of coupling anion-exchange column chromatography with radioimmunoassay},
author = {Doucet, L and De Veyrac, B and Delaage, M and Cailla, H and Bernheim, C and Devissaguet, M},
abstractNote = {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.},
doi = {10.1002/jps.2600790817},
url = {https://www.osti.gov/biblio/6172045}, journal = {Journal of Pharmaceutical Sciences; (USA)},
issn = {0022-3549},
number = ,
volume = 79:8,
place = {United States},
year = {Wed Aug 01 00:00:00 EDT 1990},
month = {Wed Aug 01 00:00:00 EDT 1990}
}