Simultaneous estimation of ivacaftor and tezacaftor in rat plasma by Liquid chromatography coupled with tandem-mass-spectrometry: Application to pharmacokinetic studies

Authors

M. Satya Venkata
A. Lakshmana Rao
M. William Carey

Abstract

Background: Ivacaftor and Tezacaftor belong to the CFTR potentiator class, in combination approved to manage cystic fibrosis. Objective: To establish a sensitive LC-MS/MS approach for the synchronized analysis of Ivacaftor and Tezacaftor and its appliance to rat pharmacokinetic investigation. Methodology: Method is developed with protein precipitation by acetonitrile and Ivacaftor-d4, Tezacaftor-d4 are used as internal standards. Separation is done on an Eclipse plus C18 analysis column (100 mm × 4.6 mm 1.8 μm) with a mobile phase consisting of 0.1% trifluoroacetic acid: acetonitrile (ratio 60:40, v/v, and pH 2.5) and flow stream of 1.0 mL/min at ambient temperature. Results: The approach developed showed fine calibration curve in the quantity range of 1.5-22.53 ng/mL (r2 – 0.99974) for ivacaftor and 1-15.02 ng/mL (r2 – 0.99988) for tezacaftor and the accuracy and precision meets F.D.A guidelines. Conclusion: The newly designed and validated approach was simple, fast and applied effectively for rat pharmacokinetic investigation.

Publisher

Faculty of Pharmaceutical Sciences, Chulalongkorn University

First Page

451

Last Page

460

Recommended Citation

Venkata, M. Satya; Rao, A. Lakshmana; and Carey, M. William (2021) "Simultaneous estimation of ivacaftor and tezacaftor in rat plasma by Liquid chromatography coupled with tandem-mass-spectrometry: Application to pharmacokinetic studies," The Thai Journal of Pharmaceutical Sciences: Vol. 45: Iss. 6, Article 3.
Available at: https://digital.car.chula.ac.th/tjps/vol45/iss6/3