title: Application of quantitative NMR for purity determination of standard ACE inhibitors.
abstract: This study investigated the accuracy of the quantitative NMR method for purity determination of ACE inhibitors reference standards and the discovery of two pairs of new diastereoisomers. Six types of ACE inhibitors, imidapril hydrochloride, benazepril hydrochloride, lisinopril, enalapril maleate, quinapril hydrochloride, and captopril were quantificated and validated for the qNMR method by discussing factors that affect parameters of the qNMR experiment, internal standards, integration, pH-effect, and uncertainty. The results were compared with data obtained by the mass balance method. The study found that maleic acid influenced the quantification of captopril in deuteroxide because of a chemical reaction. The mixtures of the reaction products were isolated by HPLC and structurally elucidated by NMR as two pairs of new diastereoisomers, 1-[(2S,4R)-thio-2-methylpropionyl-5-d-ethanedicarboxylicacid]-L-proline and 1-[(2S,4S)-thio-2-methylpropionyl-5-d-ethanedicarboxylicacid]-L-proline. The results showed that the accuracy and precision of quantitative (1)H NMR spectroscopy satisfied the requirements for quantitative analysis of chemical reference standards and provided a simple, rapid, and reliable method for purity determination of ACE inhibitors systematically.
authors.affiliation: National Institute for Food and Drug Control, Beijing 100050, People's Republic of China; National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, People's Republic of China.
authors.forename: Shi
authors.initials: S
authors.lastname: Shen
authors.affiliation: National Institute for Food and Drug Control, Beijing 100050, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yang
authors.affiliation: National Institute for Food and Drug Control, Beijing 100050, People's Republic of China. Electronic address: shiyq@nicpbp.org.cn.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis*; D001552:Benzazepines / Q000032:analysis; D002138:Calibration; D002216:Captopril / Q000032:analysis*; D002244:Carbon / Q000737:chemistry; D017666:Deuterium Oxide / Q000032:analysis; D004656:Enalapril / Q000032:analysis; D004791:Enzyme Inhibitors / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D048289:Imidazolidines / Q000032:analysis; D017706:Lisinopril / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008298:Maleates / Q000032:analysis*; D000432:Methanol / Q000737:chemistry; D000077583:Quinapril; D012015:Reference Standards; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000032:analysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D004791:Enzyme Inhibitors; D048289:Imidazolidines; D008298:Maleates; D012997:Solvents; D044005:Tetrahydroisoquinolines; D004656:Enalapril; D002244:Carbon; C030272:maleic acid; D002216:Captopril; C065166:imidapril; D017706:Lisinopril; D017666:Deuterium Oxide; D000077583:Quinapril; C044946:benazepril; D000432:Methanol
keywords: ACE inhibitors; Captopril; Diastereoisomers; Thiol-ene click reaction; qNMR