痰热清胶囊替代方与痰热清胶囊药代动力学比较研究  

Pharmacokinetic comparison between Tanreqing Capsules Substitute and Tanreqing Capsules in rats by LC-MS/MS

作　　者：赵逸宁 石荣[1] 昝斌 李园园[1] 王天明[1] 刘绍勇 杨莉[3] 马越鸣[1] ZHAO Yi-ning;SHI Rong;ZAN Bin;LI Yuan-yuan;WANG Tian-ming;LIU Shao-yong;YANG Li;MA Yue-ming(School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Kai Bao Pharmaceutical Co.,Ltd.,Shanghai 200120,China;Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中药学院,上海201203 [2]上海凯宝药业股份有限公司,上海200120 [3]上海中医药大学中药研究所,上海201203

出　　处：《中国中药杂志》2021年第20期5372-5381,共10页China Journal of Chinese Materia Medica

基　　金：国家“重大新药创制”科技重大专项(2017ZX09309006);上海市科委技术标准专项(16DZ0501000)。

摘　　要：痰热清胶囊(TRQ)中熊胆原料受限,用体外培育熊胆粉替代,研制成痰热清胶囊替代方(TRQS)。该文建立了灵敏、准确地测定大鼠血浆中TRQS多成分熊去氧胆酸(UDCA)、鹅去氧胆酸(CDCA)、牛磺熊去氧胆酸(TUDCA)、牛磺鹅去氧胆酸(TCDCA)、阿魏酸、连翘酯苷A、黄芩苷、汉黄芩苷浓度的LC-MS/MS方法,并用以评价TRQS和TRQ在大鼠体内的药动学行为。血浆样品在经蛋白沉淀后,采用Waters BEH C18色谱柱(2.1 mm×100 mm,1.7μm)分离,流动相为含0.01%甲酸的10 mmol·L^(-1)甲酸铵水溶液和乙腈-甲醇(1∶5);质谱的离子源为电喷雾电离源,在多反应监测模式下正负离子同时测定。采用D4-TUDCA、D4-TCDCA、D4-UDCA和D4-CDCA替代方法,通过响应换算系数校正,测定血浆UDCA、CDCA、TUDCA、TCDCA的浓度。结果表明血浆中各成分线性良好(r>0.9951),质控样品日内精密度RSD均小于7.0%、准确度在89.98%~112.0%,日间精密度RSD均小于12%,准确度在90.41%~111.2%,回收率在64.83%~109.9%,基质效应在87.15%~113.8%。大鼠单次灌胃给予0.94 g·kg-1后,TRQS和TRQ之间,主要成分黄芩苷、UDCA、TUDCA和TCDCA的药代动力学特征基本一致。Due to the limited resource of bear bile powder,the major raw material of Tanreqing Capsules(TRQ),cultured bear bile powder is used as a replacement to develop the Tanreqing Capsules Substitute(TRQS).An LC-MS/MS method was established in this study for simultaneous quantitation of 8 compounds from TRQS in rat plasma:tauroursodeoxycholic acid(TUDCA),taurochenodeoxycholic acid(TCDCA),ursodeoxycholic acid(UDCA),chenodeoxycholic acid(CDCA),ferulic acid,wogonoside,baicalin,and forsythoside A.Thereby,the pharmacokinetic behaviors of TRQ and TRQS were evaluated.Concentration of endogenous compounds TUDCA,TCDCA,UDCA,and CDCA was determined with the stable isotope surrogate analytes:D4-TUDCA,D4-TCDCA,D4-UDCA,and D4-CDCA.Plasma samples were extracted by acetonitrile-induced protein precipitation.The LC conditions are as follows:Waters BEH C18 column(2.1 mm×100 mm,1.7μm),mobile phase of 10 mmol·L^(-1)ammonium formate aqueous solution(contai-ning 0.01%formic acid)and acetonitrile-methanol mixture(1∶5).MS conditions are as below:multiple reaction monitoring(MRM),ESI+/-.Concentration of UDCA,CDCA,TUDCA,and TCDCA was corrected with a response factor,which is the ratio between the responses recorded for the surrogate and the authentic analyte at the equal concentration.Each of the plasma components showed good linearity(r>0.9951).Accuracy and precision met the criteria(inter-day RSD<7.0%,RE 89.98%-112.0%;intra-day RSD<12%,RE 90.41%-111.2%).The recovery was 64.83%-119.9%and matrix effect was 87.15%-113.8%.The validated method was applied for pharmacokinetic study of TRQS and TRQ(po,0.94 g·kg-1).There was no significant difference in Cmax and AUC0-24 h of baicalin,UDCA,TUDCA,and TCDCA between the two groups,indicating similar pharmacokinetic behaviors between TRQS and TRQ in rats.

关 键 词：痰热清胶囊替代方 痰热清胶囊 药代动力学 LC-MS/MS 大鼠 

分 类 号：R285.5[医药卫生—中药学]