新型抗抑郁化合物WJ-14在大鼠体内和人肝微粒体中代谢产物的HPLC-MS/MS分析  

Identification of novel anti-depressant compound WJ-14 metabolites in rats and human liver microsomes by HPLC-MS/MS

作　　者：黄卫胤 杨礼寿 张轶雯 杨小生 叶林虎 HUANG Wei-yin;YANG Li-shou;ZHANG Yi-wen;YANG Xiao-sheng;YE Lin-hu(Department of Pharmacy,Zhejiang Provincial People's Hospital Bijie Hospital,Bijie 551700,China;Natural Products Research Center of Guizhou Province,Guiyang 550014,China;State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550025,China;Department of Pharmacy,Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College,Hangzhou 310014,China;The Sixth Affiliated Hospital of South China University of Technology,Foshan 528000,China)

机构地区：[1]浙江省人民医院毕节医院药学部,毕节551700 [2]贵州省天然产物研究中心,贵阳550014 [3]贵州医科大学省部共建药用植物功效与利用国家重点实验室,贵阳550025 [4]浙江省人民医院药学部杭州医学院附属人民医院,杭州310014 [5]华南理工大学附属第六医院,佛山528000

出　　处：《药物分析杂志》2024年第12期2023-2032,共10页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金资助项目(81860609);贵州省科技计划项目(黔科合支撑[2021]一般424);毕节市科技局联合基金项目([2023]61);佛山市“十四五”医学重点专科;毕节市科技局重大专项([2023]2-1)。

摘　　要：目的:研究新型抗抑郁化合物WJ-14在大鼠体内和人肝微粒体中的代谢产物和代谢途径。方法:采用HPLC-MS/MS对大鼠血浆和尿液,以及人肝微粒体体外孵育体系样本进行分析。色谱条件:采用Hypersil BDS C_(18)(100 mm×4.6 mm,3μm)色谱柱,以含0.1%甲酸水溶液(A)-甲醇(B)为流动相,梯度洗脱,流速0.4 mL·min^(-1),柱温40℃,进样量5μL。结合WJ-14的碎裂方式和特征碎片离子对WJ-14的代谢产物进行鉴定,并推测其代谢途径。结果:共鉴定出WJ-14的代谢产物12个,大鼠体内6个,人肝微粒体中6个,其中2个代谢物在大鼠体内和人肝微粒体中都被检测到。WJ-14的代谢途径为羟基化、去甲基化、水合、葡萄糖醛酸化和甲基化。结论:利用HPLC-MS/MS技术对WJ-14的代谢产物和代谢途径进行研究,WJ-14的代谢途径包括Ⅰ相和Ⅱ相代谢,其中以Ⅰ相代谢中的羟基化为主。研究结果可为WJ-14的制剂开发和应用提供参考。Objective:To investigate the metabolites and metabolic pathways of WJ-14,a novel anti-depressant compound,in rats and human liver microsomes by HPLC-MS/MS.Methods:Samples of rat plasma and urine,as well as in vitro incubation system of human liver microsomes were analyzed by HPLC-MS/MS.Chromatographic conditions:the chromatographic conditions were as follows:Hypersil BDS C_(18)(100 mm×4.6 mm,3μm)column,with 0.1%formic acid aqueous solution(A)-methanol(B)as the mobile phase,gradient elution flow rate 0.4 mL·min^(-1),column temperature 40℃,and injection volume 5μL.The identification of metabolites and speculation on the metabolic pathways of WJ-14 were conducted by comparing the fragmentation mode and characteristic fragment ions of WJ-14.Results:A total of 12 metabolites of WJ-14 were identified,including 6 in rat and 6 in human liver microsomes,with two metabolites were detected in both rat and human liver microsomes.The major metabolic pathways of WJ-14 were identified as hydroxylation,demethylation,hydration,glucuronidation and methylation.Conclusion:In this work,we investigated the metabolites and metabolic pathways of WJ-14 using HPLC-MS/MS for the first time.The metabolism of WJ-14 occurred in phaseⅠand phaseⅡmetabolic reactions,in which hydroxylation in phaseⅠis dominant.The results of the current study may provide valuable information for the formulation development and application of WJ-14.

关 键 词：WJ-14 高效液相色谱-质谱联用技术 代谢产物 人肝微粒体 代谢途径 

分 类 号：R917[医药卫生—药物分析学]