THE THAI JOURNAL OF PHARMACEUTICAL SCIENCES

Volume 45, No. 06, Month JUNE, Year 2021, Pages 451 - 460

Simultaneous estimation of ivacaftor and tezacaftor in rat plasma by lc-ms-ms application to pharmacokinetic studies

Mamidi Satya Venkata Sakuntala, Lakshmana Rao, William Carey Mamidipalli

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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.

Keywords

Ivacaftor, Tezacaftor, LC-MS/MS, Method Validation, Pharmacokinetic study, Rat plasma

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