A Simple UPLC/MS-MS Method for Simultaneous Determination of Lenvatinib and Telmisartan in Rat Plasma, and Its Application to Pharmacokinetic Drug-Drug Interaction Study

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 4; p. 1291
• Main Authors: Cui, Yanjun, Li, Ying, Li, Xiao, Fan, Liju, He, Xueru, Fu, Yuhao, Dong, Zhanjun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.02.2022; MDPI
• Subjects: Accuracy; Acetic acid; Acetonitrile; Ammonium; Ammonium acetate; Analytical chemistry; Angiogenesis; Angiogenesis inhibitors; Angiotensin; Animals; Binding sites; Blood pressure; Calibration; Cancer therapies; Chromatography, High Pressure Liquid; Drug interaction; Drug Interactions; Drug Monitoring; Drug Stability; drug-drug interaction; Enzyme inhibitors; Formic acid; Growth factors; Hypertension; Kinases; lenvatinib; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metastasis; Molecular Structure; Pharmacokinetics; Pharmacology; Phenylurea Compounds - chemistry; Phenylurea Compounds - pharmacokinetics; Plasma; Positive ions; Protein-tyrosine kinase; Proteins; Quinolines - chemistry; Quinolines - pharmacokinetics; Rats; Reproducibility of Results; Retention; Scientific imaging; Sensitivity and Specificity; Stability analysis; Tandem Mass Spectrometry; telmisartan; Telmisartan - chemistry; Telmisartan - pharmacokinetics; Tumors; Tyrosine; UPLC-MS/MS; pharmacokinetics; UPLC-MS/MS; lenvatinib; telmisartan; drug-drug interaction
• ISSN: 1420-3049; 1420-3049
• 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.