Simultaneous determination of telmisartan and pitavastatin in rat plasma by UPLC–MS/MS: Application to pharmacokinetic interaction study

• Published in: Journal of pharmaceutical and biomedical analysis 2016-11, Vol.131, p.373-379
• Main Authors: Chen, Xi, Xu, Bei, Yang, Jian, Liu, Juan, Fang, Dailong, Gu, Yongjun, Jian, Zhifei, Tang, Minghai, Fu, Chunmei, Zhang, Zhi, Jiang, Chunling, Song, Xiangrong
• Format: Article
• Language: English
• Subjects: Animals; Benzimidazoles - blood; Benzimidazoles - pharmacokinetics; Benzoates - blood; Benzoates - pharmacokinetics; Chromatography, High Pressure Liquid - methods; Drug interaction; Female; LC–MS/MS; Male; Pharmacokinetics; Pitavastatin; Quinolines - blood; Quinolines - pharmacokinetics; Rats; Tandem Mass Spectrometry - methods; Telmisartan
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2016.09.006

[Display omitted] •A rapid LC–MS/MS method was developed for simultaneous quantitation of telmisartan and pitavastatin in a small volume of rat plasma.•The assay was developed and fully validated in rat plasma.•The method was applied to investigate the pharmacokinetic interaction of telmisartan and pitavastatin in SD rats.•Our study preliminarily proved that there was no significant drug–drug interaction between Tel and Pit in pharmacokinetic parameters for the first time. To investigate the pharmacokinetic (PK) interaction between telmisartan (Tel) and pitavastatin (Pit), a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometric assay method had been successfully established and fully validated for the simultaneous quantification of Tel and Pit in rat plasma. A simple protein precipitation procedure was adopted for the sample preparation with satisfactory extraction recovery for both analytes and the internal standard. The samples were chromatographed on an Inertsil ODS-3 C18 column (100mm×2.1mm, 2μm) using a mixture of acetonitrile and 10mM ammonium acetate containing 0.1% formic acid (60: 40, v/v) as the mobile phase at a flow rate of 0.4mL/min. The calibration curves obtained were linear (r>0.99) over the concentration range of 2–200ng/mL for Tel and 1–100ng/mL for Pit, respectively. The validated method was successfully applied to the PK study and the data did not reveal any evidence for the potential drug–drug interaction (DDI) between Tel and Pit. This information would provide the evidence for clinical rational use of Tel and Pit, and this study might be applied in therapeutic drug monitoring in patients receiving Tel/Pit combinations or single drug.