Estimation of lumacaftor, ivacaftorin by using LC-MS method and their pharmacokinetic studies

This method aims to develop a simple, cost-effective, rugged, and susceptible for the determination of Lumacaftor and Ivacaftor using LC-MS, by using Tezacaftor as an internal standard solution. Chromatographic analysis is performed by a Waters 2695 HPLC system with a high-speed autosampler. The total runtime is 7.0 minutes. The retention times for Lumacaftor, and Ivacaftorit are 4.053, 2.714 minutes respectively. The method was validated for Lumacaftor, and ICF in the range of 10-400 ng/mL, 6.25-250 ng/mL range respectively. At least 67% of samples were within the 80-120% accuracy range, with a coefficient of variation for accuracy ≤ 20%. Intra- and inter-batch %CVs across five levels were less than 15%. Benchtop stability studies indicated that the mean accuracy was within the 85.00% to 115.00% range, with a %CV of ≤ 15.00%. Auto-sampler stability showed that LLQC was within the 80.00% to 120.00% range. Freeze-thaw cycles %CV is ≤ 15.00%, with mean stability of samples wet, dry extract stability between 85.00% and 115.00%. Finally, this method is concluded for suitability for pharmacokinetic studies and routine analysis in biological samples and the usage of batch analysis release in the QC laboratory. KEY WORDS: Lumacaftor, Ivacaftor, Benchtop stability, Freeze-thaw cycles, Pharmacokinetic Bull. Chem. Soc. Ethiop. 2025, 39(10), 1977-1988. DOI: https://dx.doi.org/10.4314/bcse.v39i10.8