Development and Validation of the LC-MS/MS Method and Its Application for Pharmacokinetic Studies for the Simultaneous Estimation of Motixafortide and Filgrastim in rat Plasma.

Abstract

Listen

Translate article

Motixafortide, a CXCR4 antagonist, and filgrastim, a granulocyte colony-stimulating factor, have shown significant potential in enhancing hematopoietic stem cell mobilization and improving cancer treatment outcomes when used in combination. However, critical challenges persist due to the absence of analytical methods and the necessity for reliable quantification of both drugs in biological matrices. This research aims to address these gaps by developing and validating a liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of motixafortide and filgrastim in rat plasma. An isocratic mobile phase with acetonitrile and buffer was employed for separation, following protein precipitation with acetonitrile, using a C18 Waters X-Terra RP-18 column (150x4.6 mm,3.5 μm). Liquid chromatography-tandem mass spectrometry with an internal standard employs multiple reaction monitoring in electrospray ionization (positive ion mode) to monitor the transitions. The method was validated according to USFDA guidelines, assessing parameters such as selectivity, matrix effect, linearity, precision, accuracy, lower limit of quantification, and stability. This method was successfully applied in pharmacokinetic studies, ensuring reliable and accurate quantification of co-administered motixafortide and filgrastim. These findings significantly contribute to optimizing therapeutic protocols and enhancing treatment outcomes for cancer patients.