金红片中活性成分在正常大鼠和浅表性胃炎大鼠体内的药代动力学研究

Pharmacokinetics of active components in Jinhong tablets in normal and superficial gastritis rats

目的:基于UPLC-Q-TOF-MS/MS技术对金红片中化学成分进行成分鉴定,建立UPLC-MS/MS法测定口服给药后不同时间点主要活性成分的血药浓度,比较其在正常大鼠体内和慢性浅表性胃炎模型大鼠体内药代动力学特征的差异。方法:构建慢性浅表性胃炎大鼠模型,正常组与模型组大鼠各6只,灌胃给予金红片混悬液(mg·kg^(-1)),眼内眦取血,采用UPLC-MS/MS法测定大鼠血浆样品中延胡索甲素、延胡索乙素和莽草酸含量,使用DAS 2.0软件计算主要药动学参数。结果:金红片鉴定出54个化学成分,延胡索甲素、延胡索乙素和莽草酸在各自范围线性关系良好(r>0.9912);3个成分的日内、日间精密度在0.86%~7.8%;提取回收率在77.9%~110.6%,基质效应在92.2%~106.2%;在室温条件下存放12 h,4℃冷藏24 h,-80℃冻融3次的稳定性试验的RSD均<8.6%,符合生物样品分析要求。主要药动学参数:模型组大鼠延胡索甲素的Cmax、AUC0-t高于正常组(P<0.01,P<0.05),延胡索乙素的Cmax、AUC0-t也高于正常组(P<0.01,P<0.01),莽草酸的Cmax、AUC0-t低于正常组,T1/2、MRT长于正常组。结论:金红片在正常大鼠体内和慢性浅表性胃炎模型大鼠体内药代动力学行为存在差异,这是由于病理状态会引起体内环境的变化,对药物有效成分的吸收和代谢发生了变化。

Objective:To establish an UPLC-MS/MS method to determine the blood concentration of the main active components at different time points after oral administration,and to compare the difference in pharmacokinetics characteristics between normal rats and chronic superficial gastritis model rats and to identity the chemical components in Jinhong tablets based on UPLC-Q-TOF-MS/MS technology.Methods:A rat model of chronic superficial gastritis was established.Six rats in the normal group and six rats in the model group were given Jinhong tablets suspension(200 mg·kg^(-1))by gavage.Blood was taken from the inner canthus.The contents of corydaline,tetrahydropalmatine and shikimic acid in rat plasma samples were determined by UPLC-MS/MS,and the main pharmacokinetic parameters were calculated by DAS 2.0 software.Results:54 chemical components were identified in the Jinhong tablets.The linear relationships between corydaline,tetrahydropalmatine,and shikimic acid were good within their respective ranges(r0.9912).The intra day and inter day precision of the three components ranges from 0.86%to 7.8%.The extraction recovery rate ranges from 77.9%to 110.6%,and the matrix effect ranges from 92.2%to 106.2%.The RSD of stability tests at room temperature for 12 hours,4℃refrigeration for 24 hours,and-80℃freeze-thaw for 3 times were all less than 8.6%,meeting the requirements for biological sample analysis.Main pharmacokinetic parameters:The C_(max)and AUC_(0-t)of corydaline in the model group rats were higher than those in the normal group(P0.01,P0.05),while the C_(max)and AUC_(0-t)of tetrahydropalmatine were also higher than those in the normal group(P0.01,P0.01).The C_(max)and AUC_(0-t)of shikimic acid were lower than those in the normal group,while T_(1/2)and MRT were longer than those in the normal group.Conclusion:The pharmacokinetic behavior of Jinhong tablets in normal rats and chronic superficial gastritis model rats was different,which was due to the changes in the internal environment caused by pathological conditions,and the changes in the absorption and metabolism of effective ingredients of drugs.