Drug Development and Validation of a Sensitive Bio-analytical LCMS/MS Method for Quantification of Asciminib-a Chronic Myeloid Leukemia Drug in Human Plasma
Author(s): Govindarao Yedlapalli* and Y. Ganesh Kumar
Abstract
This study targeted to develop a reliable and less time consuming Liquid Chromatography–Mass Spectrometry/Mass spectrometry (LC–MS/MS) method for quantification of chronic myeloid leukemia drug, asciminib in human plasma using sunitinib as internal standard. The analyte asciminib and sunitinib were extracted from spiked plasma by adopting liquid-liquid extraction using methyl tertiary butyl ether solvent and chromatographed on an Alltima HP C18 (100 mm × 4.6 mm, 3 μm) column with pH 4.3 ammonium formate (5 mM) buffer and methanol in 45 (v/v):55 (v/v) at pH 4.3 mL/min at 1.0 mL/min flow in isocratic mode. The analysis completed within a total chromatographic run time of 4 min that facilitates less time and solvent consumption. The column separated analytes were recorded using mass detector with positive ion electrospray ionization source. The mass spectrum shows precursor-to-product ion transitions at m/z of 450/195 (m+1) for asciminib and 399/185 (m+1) for sunitinib. The method produces calibration curve linear in 2.5 ng/mL-200 ng/mL concentration range with sensitive detection limit of 0.075 ng/mL for asciminib. The mean plasma spiked extraction recoveries of both asciminib and internal standard was very high with acceptable % RSD in all precision studies. The analytes were noticed to be stable in a variety of stability studies performed. The method was validated to be sensitive, accurate and was suitable for determination of asciminib in human plasma and applicable for regular quality analysis studies.
