A sensitive bioanalytical method development and validation of cabozantinib in human plasma by LC-ESI-MS/MS

Abstract

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of cabozantinib (CZ) in human plasma using cabozantinib-d4 (CZD4) as an internal standard (IS). Chromatographic separation was performed on Xbridge C18, 50 x 4.6 mm, 5 mm column with an isocratic mobile phase composed of 10mM Ammonium formate and Methanol in the ratio of (20:80 v/v), at a flow-rate of 0.7 mL/min. CZ and CZD4 were detected with proton adducts at m/z 502.2 → 391.1 and 506.3 → 391.2 in multiple reaction monitoring (MRM) positive mode respectively. Liquid-Liquid extraction method was used to extract the drug and IS. The method was validated over a linear concentration range of 5.0-5000.0 pg/mL with correlation coefficient (r 2) ≥ 0.9994. This method demonstrated intra and inter-day precision within 1.95 to 2.37 and 2.93 to 9.3 % and Accuracy within 101.4 to 102.4 and 99.5 to 104.8 %. Cabozantinib was found to be stable throughout freeze-thawing cycles, bench top and postoperative stability studies.

Pharmacokinetic Investigation of Remogliflozin in Rat Plasma Samples by High-Throughput HPLC-MS-MS

“…The percent CV of matrix factor for at MQC level of REMO was found to be 1.96. The percent CV value indicated that there was no significant effect of the matrix on the bio-analytical methodology for simultaneous evaluation of REMO [22].…”