P-糖蛋白（P-gp）介导的草药-药物相互作用（HDI）可能会影响药物的功效和安全性。 Tenacissoside G (Tsd-G) 是 Marsdenia tenacissima 的主要活性成分，具有抗癌活性。为了分析 Tsd-G 对紫杉醇 (PTX) 药代动力学的影响，研究人员选择了 30 只 Sprague-Dawley (SD) 大鼠，随机分为溶剂对照组、维拉帕米阳性对照组和 20、40 和 60mg/ kg Tsd-G 组。连续7天腹腔注射维拉帕米或Tsd-G后，静脉注射单剂量6mg/kg PTX。在不同时间点收集血浆样品，并使用甲醇-乙腈溶液沉淀蛋白质。建立了以多西紫杉醇为内标，采用正离子多反应监测（MRM）模式进行定量的超高效液相色谱-串联质谱方法。该分析方法的专属性、准确度、精密度、回收率、基质效应和样品稳定性满足生物样品测定的要求。大鼠给药Tsd-G后，PTX的平均停留时间显着延长。并且Tsd-G可以通过形成氢键稳定地与P-gp结合并抑制大鼠肝脏中P-gp的表达。虽然本研究中没有检测到 PTX 的代谢产物，但上述结果仍然表明 Tsd-G 和 PTX 之间存在 HDIs，并且 P-gp 可能是介导 HDIs 的主要靶点。© 2024 John Wiley

P-glycoprotein (P-gp)-mediated herb-drug interactions (HDIs) may impact drug efficacy and safety. Tenacissoside G (Tsd-G), a major active component of Marsdenia tenacissima, exhibits anticancer activity. To analyze the effect of Tsd-G on the pharmacokinetics of paclitaxel (PTX), researchers selected 30 Sprague-Dawley (SD) rats, randomized into a solvent control group, a verapamil positive control group, and 20, 40, and 60 mg/kg Tsd-G groups. After seven consecutive days of intraperitoneal injection of verapamil or Tsd-G, a single dose of 6 mg/kg PTX was injected intravenously. Plasma samples were collected at different time points, and proteins were precipitated using a methanol-acetonitrile solution. An ultrahigh-performance liquid chromatography-tandem mass spectrometry method was developed, with docetaxel as an internal standard, and quantified using positive ion multiple reaction monitoring (MRM) mode. This analytical method's specificity, accuracy, precision, recovery, matrix effect, and sample stability meet the requirements for biological sample determination. After Tsd-G administration in rats, the mean residence time of PTX was significantly prolonged. And Tsd-G can stably bind to P-gp by forming hydrogen bonds and inhibiting the expression of P-gp in rat liver. Although the metabolites of PTX were not detected in this study, the above results still indicate the existence of HDIs between Tsd-G and PTX, and P-gp may be the main target to mediate HDIs.© 2024 John Wiley & Sons Ltd.