Development and Validation of Liquid Chromatography–Tandem Mass Spectrometry Method for Quantification of Lazertinib in Plasma Samples and Pharmacokinetic Study in Rabbits

Abstract

The aim of the present study was to establish a precise, linear, and specific liquid chromatography‐electrospray ionization‐tandem mass spectrometry (LC–ESI–MS/MS) technique for the quantitative estimation of lazertinib in plasma of rabbits. Analyte separation was accomplished on a Phenomenex C18 (50 × 4.6 mm, 2.1 µm) column, employing an isocratic mobile phase composed of 0.1% formic acid and methanol (15:85, v/v), with a 0.6 mL/min flow rate. Detection was performed in LC–ESI–MS/MS by multiple reaction monitoring specimode, with ionic transitions m/z 555.27 → 501.27 for lazertinib and m/z 494.27 → 451.23 for imatinib, which was utilized as the internal standard. A lower limit of quantification of 13 ng/mL was established with excellent selectivity, enabling efficient separation of lazertinib from endogenous plasma components under optimized LC–MS/MS conditions. Linearity standards were performed at 13–520 ng/mL, and the regression analysis yielded y = 0.0028 x + 0.0038, with r 2 value of 0.9998. The matrix effect showed %CV values of 3.40% (low quality control [low‐QC]) and 3.70% (high‐QC). The mean recovery values for lazertinib were 95.29% at high‐QC (390 ng/mL), 96.84% at mid‐QC (260 ng/mL), and 94.33% at low‐QC (36.4 ng/mL). Precision results for QC levels ranged from 2.00% to 4.03%, well within acceptance limits. Negligible carry‐over was observed, and the analyte demonstrated acceptable stability under all evaluated storage and processing conditions. After being administered to rabbits, the validated technique was tested for lazertinib's pharmacokinetic properties. T max , C max , and T 1/2 of the lazertinib formulation were 2 ± 0.02 h, 440.12 ± 14.60 ng/mL, and 2.195 ± 0.05 h, respectively. AUC 0‐∞ for the lazertinib formulation was 1220.515 ± 49.10 ng/mL·h. The developed technique was subjected to method validation as per the US Food and Drug Administration bioanalytical guidelines and demonstrated suitability for the routine quantification of lazertinib in plasma and pharmacokinetic assessment in rabbits.