金振口服液的2种成分在大鼠体内的药动学  

Pharmacokinetics of two components of Jinzhen oral liquid in rats

作　　者：高霞[1,2] 王善丽 王佳佳 高惠芳 钱梦雨 童孝宇 陈夏霖 张全昌 曹亮[1,2] 王振中[1,2] 肖伟[1,2] GAO Xia;WANG Shan-li;WANG Jia-jia;GAO Hui-fang;QIAN Meng-yu;TONG Xiao-yu;CHEN Xia-lin;ZHANG Quan-chang;CAO Liang;WANG Zhen-zhong;XIAO Wei(Jiangsu Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China;State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process,Lianyungang 222001,China;China Pharmaceutical University,Nanjing 211199,China)

机构地区：[1]江苏康缘药业股份有限公司,连云港222001 [2]中药制药过程新技术国家重点实验室,连云港222001 [3]中国药科大学,南京211199

出　　处：《中国新药杂志》2023年第5期522-530,共9页Chinese Journal of New Drugs

基　　金：江苏省工信厅2020年度工业和信息产业转型升级专项资金项目:多组分中药研究关键技术。

摘　　要：目的:评估金振口服液单次和多次服用后药动学特征和吸收代谢差异。方法:运用超高效液相色谱-三重四级杆质谱联用(UPLC-TSQ-MS)技术,建立同时定量大鼠血浆中黄芩苷和汉黄芩苷的分析方法。将健康大鼠分别按3.228,6.456,12.912 g生药量·kg^(-1)单次灌胃(ig)和按6.456 g生药量·kg^(-1)多次ig金振口服液,测定不同时间血浆中待测成分含量,运用非房室模型计算药动学参数。结果:血浆样品中2种成分的线性关系良好(r>0.995),提取回收率和基质效应的RSD均<15%,批内、批间的精密度和准确度以及稳定性均符合生物样品分析要求。大鼠单次给药后,黄芩苷和汉黄芩苷的AUC0-t均与剂量呈良好的正相关性,且不同剂量下t1/2z和清除率(CLz/F)无显著变化;与单次给药相比,多次给药后大鼠的吸收代谢过程基本相同、AUC0-t和t1/2z差异无统计学意义。结论:本研究建立了稳定可靠的黄芩苷和汉黄芩苷UPLC-TSQ-MS定量方法,在3.228~12.912 g生药量·kg^(-1)范围内金振口服液中2种成分在体内呈现线性动力学的特征,多次给药后无蓄积现象,揭示该制剂临床剂量的合理性。Objective:To evaluate the pharmacokinetic characteristics of Jinzhen oral liquid and compare the difference of the absorption and metabolism after single and multiple administrations in rats.Methods:An ultra-high performance liquid chromatography coupled to triple-stage quadrupole mass spectrometer(UPLC-TSQ-MS)was applied to established the method for simultaneous determination of baicalin and wogonoside in rat plasma.Healthy rats were administered a single dose(3.228,6.456,and 12.912 g·kg^(-1))and multiple dose(6.456 g·kg^(-1))of Jinzhen oral liquid(crude drug)by oral gavage.The content of target components in plasma at different time points was determined,and the pharmacokinetic parameters were calculated using the non-compartmental model.Results:The two components in the plasma sample have good linear relation(r>0.99).RSDs of their extraction recovery rate and matrix effect are both<15%,the intra-and inter-batch precision and accuracy,and stability meet the requirements of biological sample analysis.After single administration of Jinzhen oral liquid,the areas under the concentration-time curve AUC(0-t)of baicalin and wogonoside show a good positive correlation with dose(R~2>0.9),and their t1/2zand CLz/F have no significant difference at different doses.Compared with a single administration,their absorption and metabolism process are basically the same,and their AUC(0-t)and t1/2zhave no significant difference after multiple administration.Conclusion:A stable and reliable UPLC-TSQ-MS quantitative method for baicalin and wogonoside was established.And two components of Jinzhen oral liquid show linear dynamics characteristics in rats between 3.228 and 12.912 g·kg^(-1)(crude drug),and there is no accumulation after multiple administrations,revealing the rationality of the clinical dosage of the preparation.

关 键 词：金振口服液 药动学 超高效液相色谱-三重四级杆质谱联用 黄芩苷 汉黄芩苷 

分 类 号：R963[医药卫生—微生物与生化药学]