Development of a Rapid LC-MS/MS Method and Its Application for the Pharmacokinetic Analysis of Pacritinib in Rats

Pacritinib is a novel medication with certain limitations and unknowns in therapeutic applications. Due to the increased frequency of side effects such as fungal infections, nausea, and vomiting, the potential for drug interactions is significantly heightened. This study aimed to establish a quantitative analysis method for pacritinib and investigate its interactions with other drugs. A quantitative detection method for pacritinib in rat plasma was developed using LC-MS/MS, with ibrutinib as an internal standard. This method was subsequently applied to pharmacokinetic and drug-drug interaction studies in rats. The method demonstrated good linearity within the range of 1-1500 ng/mL, with an LLOQ of 1 ng/mL. Both intraday and interday precisions (RSD%) were less than 14.52%, and the recovery, matrix effect, and stability met FDA guidelines. The method proved effective for the quantitative detection of pacritinib in rat plasma. Pharmacokinetic studies revealed that isavuconazole significantly inhibited the metabolism of pacritinib compared to voriconazole, resulting in a 2.5-fold increase in AUC_(0-t), a 2.6-fold increase in AUC_(0-∞), and a 3.0-fold increase in C_max. Additionally, the CLz/F value in the isavuconazole group decreased by 67%. This study successfully established a reliable LC-MS/MS method for detecting pacritinib plasma concentrations in rats. The findings indicate that isavuconazole is more likely to increase pacritinib blood exposure than voriconazole, highlighting the need for caution when combining isavuconazole with pacritinib in clinical practice.