Validated HPLC-UV Method For Quantification Of Paxalisib, A Pan Pi3k And mTOR Inhibitor In Mouse Plasma: Application To A Pharmacokinetic Study In Mice

By Ashok Zakkula, Rama Murthi Bestha, A. B. Vinod, Vinay Kiran, Sreekanth Dittakavi, and Ramesh Mullangi, Drug Metabolism and Pharmacokinetics, LAXAI, and Harsha K. Tripathy, Karnataka College of Pharmacy

Glioblastoma is the most common and aggressive form of brain cancer. Paxalisib is a pan-PI3K and mTOR inhibitor currently entering into Phase II clinical trials as a potential drug to treat glioblastoma patients, and the interim data suggest that it improves overall survival. Paxalisib has shown significant tumor growth inhibition in U87 and GS2 mice orthotopic models with 90% suppression of the pAkt signal.

However, there is no bioanalytical method reported for the quantification of paxalisib in any biological matrix. Analytical methods such as mass spectrometry is often too expensive and difficult to maintain for many hospitals and research institutions. Utilizing a high-performance liquid chromatography (HPLC) method offers a more affordable, manageable alternative. This White Paper explores the development and validation of an HPLC method for the quantitation of paxalisib in mouse plasma and its potential use for routine therapeutic drug monitoring in hospitals and in research laboratories for preclinical purposes.