Development and validation of an LC-MSMS method for the quantitation of pacritinib; application of kinetics in rabbits

Abstract

Background

Accurate and selective LC/ESI-MSMS method development and validation for the quantitation of pacritinib is the primary goal of this study to perform kinetic studies in the healthy rabbit.

Methods

Chromatographic resolution was accomplished with a hypersil/ODS (50 mm × 4.6 mm, 3 μ) analytical C₁₈ column and a mobile phase composition of 0.1% formic acid and ACN in the proportion of 25:75 with a 0.6 ml/min flow of the mobile phasic system from the analytical column. The method was employed by monitoring the established ionic transitions of m/z-473.25/98.09 for Pacritinib and 506.18/57.12 for the internal standard (Amprenavir) in multiple reaction monitoring.

Results

The calibration plot regression line was y = 0.0002× + 0.007, with a correction coefficient (r²) of 0.9989. The CV outcomes for the matrix effect at low-QC and high-QC levels were 4.79% and 4.91%, respectively. The percentage average recoveries for Pacritinib in High-QC (12.70 μg/ml), MQC (8.50 μg/ml), and Low-QC (1.19 μg/ml) were 95.87%, 103.64%, and 94.32%, respectively. The obtained values were found between 2.98 and 5.07% for the QC (1.19, 8.50, and 12.70 μg/ml) samples. The established procedure was subjected to kinetics study of Pacritinib after oral administration in rabbits. C_max, T_max, and T_1/2, of the Pacritinib tablets were 247.25 ± 3.32 ng/ml, 6.0 ± 0.03 h, and 12.24 ± 0.53 h, respectively. AUC_0-∞ infinity for Pacritinib tablets was 1691.74 ± 3.67 ng h/ml.

Conclusion

After oral administration of Pacritinib to healthy rabbits, pharmacokinetic characteristics were presented, and the established technique was effectively verified.