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)

• Record Type: Journal Article
• Authors: Li, Hua; Wang, Yang; Chen, Xuefei; Chen, Chen; Cui, Jianxin; Han, Ying; Ding, Lieming
• Is Part Of: Biomedical chromatography. Volume 37:Number 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2023-03-17
• Subjects: ensartinib -- HPLC–MS/MS -- human plasma -- method validation -- pharmacokinetics; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.5610
• Languages: English
• ISSNs: 0269-3879

Abstract

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.