Abstract Alpelisib (BY719) is a phosphoinositide-3-kinase inhibitor that specifically targets phosphoinositide-3-kinase-alpha. This enzyme is part of the phosphoinositide-3-kinase/α-serine/threonine-protein kinase/mammalian target of rapamycin signaling pathway, which promotes cell growth and survival. Mutations in the phosphoinositide-3-kinase gene cause the phosphoinositide-3-kinase signaling pathway to become overactive, leading to uncontrolled cell growth and survival, which contributes to tumor development. By inhibiting phosphoinositide-3-kinase-alpha, alpelisib can slow tumor growth and kill cancer cells. The goal of this study was to develop and validate a new, sensitive, specific, and rapid liquid chromatography–tandem mass spectrometry method for measuring alpelisib in dried blood spots from both mice and humans. Filgotinib served as the internal standard, and all procedures adhered to regulatory standards. Alpelisib and the internal standard were measured using a Sciex triple quadrupole mass spectrometer in multiple reaction monitoring mode with positive-ion detection. The focus was on the parent–daughter mass-to-charge transitions of m/z 442.0→327.9 for alpelisib and m/z 426.2→291.2 for the internal standard. The linear range for alpelisib was 0.331–1026 ng/mL (r>0.990). This method successfully characterized the in vitro metabolic profiles and in vivo pharmacokinetics of alpelisib in mice. A strong correlation was found between dried blood spots and plasma concentrations, suggesting that dried blood spots can serve as an alternative to plasma for pharmacokinetic analysis.
Dixit et al. (Tue,) studied this question.