UPLC-MS/MS 法研究白花丹素和他泽司他丁在大鼠体内的药代动力学及相互作用。
Pharmacokinetics of Herb-Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS.
机构信息
Department of Pharmacy, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People's Republic of China.
Functional Experiment Teaching Center, School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, 471023, People's Republic of China.
出版信息
Drug Des Devel Ther. 2022 Sep 29;16:3385-3394. doi: 10.2147/DDDT.S384156. eCollection 2022.
OBJECTIVE
A sensitive and rapid UPLC-MS/MS method for determination of tazemetostat in rat plasma was developed, and the pharmacokinetics of herb-drug interactions (HDIs) of plumbagin (PLB) and tazemetostat was investigated.
METHODS
After the rat plasma samples were precipitated by acetonitrile, tazemetostat and verubecestat (ISTD) were detected. Gradient elution was performed with 0.1% formic acid and acetonitrile as mobile phases. The multi-reaction monitoring was used with ESI+ source, and the ion pairs for tazemetostat and ISTD were 573.12→135.99 and 410.10→124.00, respectively. 12 SD rats were randomly divided into the control group and the experimental group, 6 rats in each group. The rats in the experimental group were given PLB 100 mg/kg by gavage once a day for 7 consecutive days. The rats in the control group were given the same amount of 0.1% sodium carboxymethyl cellulose solution by gavage once a day for 7 consecutive days. At the seventh day, tazemetostat (80 mg/kg) was given and the blood was collected at different time points. The main parameters of pharmacokinetics were calculated and the herb-drug interactions (HDIs) were evaluated.
RESULTS
In the calibrated range of 1-1000 ng/mL, tazemetostat had a good linearity. The extraction recovery was more than 84%, and the RSD of intra-batch and inter-batch precision were both less than 15%. The C of tazemetostat in the experimental group was 32.48% higher than that in the control group, and the AUC and AUC of tazemetostat in the experimental group were 46.24% and 46.67% higher than that in the control group, respectively, and the t was prolonged from 10.56 h to 11.73 h.
CONCLUSION
A simple, rapid and sensitive UPLC-MS/MS method for the determination of tazemetostat in rat plasma was established. PLB can inhibit the metabolism of tazemetostat and increase the plasma exposure of tazemetostat in rats.
目的
建立一种灵敏、快速的 UPLC-MS/MS 法测定大鼠血浆中的他泽司他，并研究百两金素（PLB）与他泽司他的草药-药物相互作用（HDIs）的药代动力学。
方法
大鼠血浆样品经乙腈沉淀后，检测他泽司他和维鲁布昔（ISTD）。采用 0.1%甲酸和乙腈为流动相进行梯度洗脱。采用 ESI+源，多反应监测，他泽司他和 ISTD 的离子对分别为 573.12→135.99 和 410.10→124.00。将 12 只 SD 大鼠随机分为对照组和实验组，每组 6 只。实验组大鼠每天灌胃 100mg/kg 的 PLB，连续 7 天。对照组大鼠每天灌胃相同体积的 0.1%羧甲基纤维素钠溶液，连续 7 天。第 7 天，给予他泽司他（80mg/kg），并在不同时间点采集血液。计算药代动力学主要参数并评价草药-药物相互作用（HDIs）。
结果
在 1-1000ng/mL 的校准范围内，他泽司他具有良好的线性关系。提取回收率大于 84%，批内和批间精密度的 RSD 均小于 15%。实验组大鼠的他泽司他 C 比对照组高 32.48%，实验组大鼠的 AUC 和 AUC 分别比对照组高 46.24%和 46.67%，t 从 10.56h 延长至 11.73h。
结论
建立了一种简单、快速、灵敏的 UPLC-MS/MS 法测定大鼠血浆中的他泽司他。PLB 可抑制他泽司他的代谢，增加大鼠血浆中他泽司他的暴露量。
Zotero 插件