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Development and Validation of an LC-MS/MS Method for Quantitative Determination of EAI045, A Novel EGFR Inhibitor, in Rat Plasma

Author(s):

Zixuan Chu, Mingxing Xue and Shan Xiong*   Pages 1 - 7 ( 7 )

Abstract:


Background: EAI045 is the fourth-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), which can overcome the acquired resistance to the third-generation EGFR TKIs and is the first allosteric inhibitor that targets T790M and C797S EGFR mutants.

Methods: A rapid and sensitive LC-MS/MS method was established and validated for the quantification of EAI045 in rat plasma. Chromatographic separation was carried out at 25°C on a Hypersil GOLD C18 column (50 mm × 2.1 mm, 5µm) and eluted on a gradient mobile phase of water (containing 0.1% formic acid) and acetonitrile at a flow rate of 0.5 mL/min. The mass spectrometer was operated in the positive ESI mode and selected reaction monitoring mode.

Results: The assay was validated over concentration range of 1.0 - 1000 ng/mL for EAI045 with a lower limit of quantification (LLOQ) of 1.0 ng/mL. The intra- and inter-batch accuracy for the EAI045 ranged from 92.25% to 97.18% and 95.94% to 102.69%, and the intra- and inter-batch precision for the EAI045 ranged from 1.41% to 4.57% and 5.18% to 6.37%, respectively. The extraction recovery, matrix effect and stability met all requirements of the guidelines for bioanalytical method validation.

Conclusion: The rapid and sensitive LC-MS/MS method was successfully applied in a pharmacokinetic study of EAI045 following oral administration (5 mg/kg) to rats.

Keywords:

EAI045, cancer, epidermal growth factor receptor tyrosine kinase inhibitor, LC-MS/MS, pharmacokinetic study, rat

Affiliation:

School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan 250200, P.R., Shandong Yantong Pharmaceutical Technology Co, . Ltd, Jinan 250014, P.R., Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062, P.R.China; c Key Laboratory for Biotech-Drugs Ministry of Health, Jinan 250062, P.R.



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