title: Radioimmunoassays for spirapril and its active metabolite spiraprilate: performance and application.
abstract: Radioimmunoassays for a nonsulfhydryl angiotensin converting enzyme inhibitor prodrug--spirapril--and its active metabolite--spiraprilate--are described. Nonextraction equilibrium assays using antibodies with a high specificity for spirapril or spiraprilate were used, with charcoal separation of bound and free tracer. Within-assay reproducibility (CV%) was less than 20% in the concentration range 0.5-40 micrograms/L for both analytes and the comparable value for between-assay reproducibility was less than 25%. Results for external quality control samples were in good agreement with the expected values of 0-250 micrograms/L (spirapril, r = 0.997) and 0-300 micrograms/L (spiraprilate, r = 0.999). Overall, samples circulated to four laboratories gave good agreement for measured values, including one center using gas chromatography-mass spectrometry analysis for the two compounds. Data are presented to show the suitability of these two assays to the measurement of spirapril and spiraprilate in clinical samples from assays to the measurement of spirapril and spiraprilate in clinical samples from dose-ranging and bioequivalence studies. Results are also shown relating drug plasma concentration data to a measurement of the pharmacodynamic effects of spiraprilate, namely inhibition of angiotensin converting enzyme activity. It is concluded that these assays have the sensitivity for use in studies to model the relationship between the pharmacokinetics and pharmacodynamics of the two compounds.
authors.affiliation: Analytical Unit, St. George's Hospital Medical School, London, England.
authors.forename: M
authors.initials: M
authors.lastname: Hossein-Nia
authors.forename: A H
authors.initials: AH
authors.lastname: Surve
authors.forename: R
authors.initials: R
authors.lastname: Weglein
authors.forename: C
authors.initials: C
authors.lastname: Gerbeau
authors.forename: D W
authors.initials: DW
authors.lastname: Holt
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis* / Q000276:immunology; D000918:Antibody Specificity; D002021:Buffers; D002606:Charcoal; D003429:Cross Reactions; D003911:Dextrans; D004656:Enalapril / Q000031:analogs & derivatives* / Q000032:analysis / Q000276:immunology; D006801:Humans; D011786:Quality Control; D011863:Radioimmunoassay; D012015:Reference Standards; D012710:Serum Albumin, Bovine / Q000276:immunology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002021:Buffers; D003911:Dextrans; D002606:Charcoal; D012710:Serum Albumin, Bovine; D004656:Enalapril; C052555:spirapril; C076884:spiraprilat