An Lc-Ms/Ms Method Development and Validation for the Quantification of Lurbinectedin in Biological Matrices; Application to Kinetic Study in Rabbits

Abstract

Objective: The primary objective of the present research was to develop an accurate liquid chromatography and tandem mass spectrometry (LC-MS/MS) technique utilizing electrospray ionization for the quantification of Lurbinectedin in biological matrices. Methods: The components were isolated using chromatographic techniques on a Hypersil Gold (50 mm×4.6 mm, 5µ) C18 column. The volume of injection was established at 5μl. The column oven temperature and flow rate were maintained at 25 °C and 0.50 ml/min, respectively. Isocratic method of separation was executed with a mobile phase composition of formic acid (0.1%), acetonitrile, and methanol in a ratio of 10:20:70 (%v/v/v). Results: In the context of multiple reaction monitoring, the observed fragments and product ions findings were recorded at m/z 785.28/174.09 for Lurbinectedin and 450.11→257.10 for the Asciminib internal standard. The linearity graph for the drug exhibited an r2 value exceeding 0.99 and demonstrated a rectilinear relationship across the concentrations in between 0.01 and 200ng/ml. Precision findings within a single day ranged from %RSD of 3.12% to 4.85%, while across different experimental days, precision values varied between 2.96% and 5.01%. The average Lurbinectedin recoveries ranged between 93.83% to 102.36% at three quality control levels. Conclusion: The findings regarding accuracy, specificity, sensitivity, matrix effect, recovery and stability findings of Lurbinectedin in plasma samples for the established method highlight its significance in bioequivalence and pharmacokinetic studies.