Development and Validation of an LC-MS/MS Method for AC1LPSZG and Pharmacokinetics Application in Rats.

Abstract

Promising preliminary clinical data have stimulated research on the use of the mammalian target of rapamycin (mTOR) inhibitors in lung cancer. AC1LPSZG is an mTOR inhibitor that can significantly reduce the viability in lung adenosquamous carcinoma cell line HTB-178 cells, showing potential benefits in effective control of non-small cell lung carcinomas. In this study, a sensitive LC-MS/MS analytical method for quantification of AC1LPSZG has been developed and optimized to a running time of 3min per sample. A linear dose-response for quantification was observed over the range of 10-5000ng/mL in rat plasma with required precision and accuracy. High extraction recovery was achieved in the ranges of 86.87-102.51% at QC levels from rat plasma without significant matrix effect. Stability profile of AC1LPSZG in rat plasma and in extract after protein precipitation suggested that samples should be processed within 6h after collection and stored at -80°C until analysis within 30days. The method was successfully applied to plasma pharmacokinetics (PK) study of AC1LPSZG in rat, showing the plasma drug concentration followed a two-compartment model.