LIU Yi, TAO Ting, LIU Yun, et al. Preparation of active thiol metabolite of clopidogrel by isolated rat liver perfusion[J]. China Pharmacy, 2022,33(14).
LIU Yi, TAO Ting, LIU Yun, et al. Preparation of active thiol metabolite of clopidogrel by isolated rat liver perfusion[J]. China Pharmacy, 2022,33(14).DOI:
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.
关键词
离体大鼠肝脏灌流氯吡格雷活性巯基代谢物制备纯化(S)-2-氧氯吡格雷
Keywords
isolated rat liver perfusionClopidogrelactive thiol me tabolitePreparationPurification(S)-2-oxo-clopidogrel