Preparation of active thiol metabolite of clopidogrel by isolated rat liver perfusion / 中国药房

ABSTRACT

OBJECTIVE To estab lish the pre paration method of clopidogrel active thiol metabolite （CATM），and to provide reference for the synthesis of cis-CATM. METHODS CATM was prepared ，separated and purified with isolated rat liver perfusion and ChromCore 120 C18 preparative column ，using（S）-2-oxo-clopidogrel as substrate. The target compounds were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The retention time of the active configuration of CATM in the human body （cis-CATM）were compared to confirm the proportion of active configuration in the target product. RESULTS The conversion rate of the target product was 11.71％. The target products were identified as CATM by MS and 1H-NMR. Peak 2-peak 5 of CATM were four stereoisomers. The retention time of them were 21.3，22.3，26.5，27.3 min. The peak area ratios of them were 7.13％，7.23％，63.52％，14.97％，respectively. Based on that retention time of the active configuration of CATM in human body was 26.3 min，the active cis-stereoisomer in the target product CATM accounted for 63.52％. CONCLUSIONS This method is low-cost ，simple，and can prepare CATM with higher active configuration.