Development of HPLC–MS/MS assay for quantitation of ensartinib in human plasma and its application to a pharmacokinetics study in Chinese patients. (17th March 2023) - Li, Hua
Abstract: Ensartinib is a novel anaplastic lymphoma kinase (ALK) inhibitor with potent activity against a broad range of known crizotinib‐resistant ALK mutations and is developed to treat patients with non‐small‐cell lung cancer. This study was the first to develop and validate a rapid and sensitive HPLC–MS/MS method for the determination of ensartinib in human plasma. The plasma samples were extracted using liquid extraction, and chromatographic separation was performed using a Phenomenex, Luna phenyl‐hexyl column (50 × 2.0 mm, 5 μm). Electrospray ionization in positive‐ion mode and multiple reaction monitoring were used to monitor ion transitions at m / z 561.3 → 257.1 (ensartinib) and 565.2 → 261.2 (internal standard: X‐396‐d4), respectively. The method yielded excellent linearity in the range of 0.5–500 ng/ml with the lowest quantification of 0.5 ng/ml. Both intra‐ and inter‐run precisions (relative standard deviation %) were less than 15%, with accuracy (relative error %) between ±15%. Extraction recovery, matrix effect, selectivity, and stability were also validated and found to be satisfactory. Finally, the validated method was successfully applied in a phase I clinical study of ensartinib in Chinese subjects with advanced ALK‐positive non‐small‐cell lung cancer.