中国中药杂志

2021, v.46(20) 5372-5381

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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

赵逸宁;石荣;昝斌;李园园;王天明;刘绍勇;杨莉;马越鸣;
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 Kai Bao Pharmaceutical Co., Ltd.;Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine;

摘要(Abstract):

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 C_(18)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>0.995 1),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), taurocheno-deoxycholic 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 C_(18) column(2.1 mm×100 mm, 1.7 μm), mobile phase of 10 mmol·L~(-1) ammonium formate aqueous solution(containing 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 > 0.995 1). 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 C_(max) and AUC_(0-24 h) of baicalin, UDCA, TUDCA, and TCDCA between the two groups, indicating similar pharmacokinetic behaviors between TRQS and TRQ in rats.

关键词(KeyWords): 痰热清胶囊替代方;痰热清胶囊;药代动力学;LC-MS/MS;大鼠
Tanreqing Capsules Substitute;Tanreqing Capsules;pharmacokinetics;LC-MS/MS;rat

Abstract:

Keywords:

基金项目(Foundation): 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)

作者(Author): 赵逸宁;石荣;昝斌;李园园;王天明;刘绍勇;杨莉;马越鸣;
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 Kai Bao Pharmaceutical Co., Ltd.;Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine;

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