National Clinical Drug Monitoring Center, Department of Pharmacy, Hebei Province General Center, Shijiazhuang 050051, China.
Department of Pharmacy, Hebei General Hospital, Shijiazhuang 050051, China.
Molecules. 2022 Feb 15;27(4):1291. doi: 10.3390/molecules27041291.
Lenvatinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis, but hypertension is the most common adverse reaction. Telmisartan is an angiotensin receptor blocker used to treat hypertension. In this study, a simple ultra-performance liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of lenvatinib and telmisartan, and it was applied to the pharmacokinetic drug interaction study. Plasma samples were treated with acetonitrile to precipitate protein. Water (containing 5 mM of ammonium acetate and 0.1% formic acid) and acetonitrile (0.1% formic acid) were used as the mobile phases to separate the analytes with gradient elution using a column XSelect HSS T3 (2.1 mm × 100 mm, 2.5 μm). Multiple reaction monitoring in the positive ion mode was used for quantification. The method was validated and the precision, accuracy, matrix effect, recovery, and stability of this method were reasonable. The determination of analytes was not interfered with by other substances in the blank plasma, and the calibration curves of lenvatinib and telmisartan were linear within the range of 0.2-1000 ng/mL and 0.1-500 ng/mL, respectively. The results indicate that lenvatinib decreased the systemic exposure of telmisartan. Potential drug interactions were observed between lenvatinib and telmisartan.
仑伐替尼是一种多靶点酪氨酸激酶抑制剂，可抑制肿瘤血管生成，但最常见的不良反应是高血压。替米沙坦是一种用于治疗高血压的血管紧张素受体阻滞剂。本研究建立了一种同时测定仑伐替尼和替米沙坦的超高效液相色谱-串联质谱法，并将其应用于药代动力学药物相互作用研究。血浆样品用乙腈沉淀蛋白。采用水（含 5 mM 醋酸铵和 0.1%甲酸）和乙腈（0.1%甲酸）作为流动相，在 XSelect HSS T3 柱（2.1mm×100mm，2.5μm）上采用梯度洗脱分离分析物。采用正离子模式下的多重反应监测进行定量分析。该方法经过验证，具有合理的精密度、准确度、基质效应、回收率和稳定性。空白血浆中其他物质对分析物的测定没有干扰，仑伐替尼和替米沙坦的校准曲线分别在 0.2-1000ng/mL 和 0.1-500ng/mL 范围内呈线性。结果表明，仑伐替尼降低了替米沙坦的全身暴露。观察到仑伐替尼和替米沙坦之间存在潜在的药物相互作用。
