1. Academic Validation
  2. To quantify the small-molecule kinase inhibitors ceritinib, dacomitinib, lorlatinib, and nintedanib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry

To quantify the small-molecule kinase inhibitors ceritinib, dacomitinib, lorlatinib, and nintedanib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry

  • J Pharm Biomed Anal. 2021 Jan 30;193:113733. doi: 10.1016/j.jpba.2020.113733.
G D Marijn Veerman 1 Peter de Bruijn 2 Anne-Marie C Dingemans 3 Ron H J Mathijssen 2 Stijn L W Koolen 4
Affiliations

Affiliations

  • 1 Department of Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands. Electronic address: g.veerman@erasmusmc.nl.
  • 2 Department of Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
  • 3 Department of Pulmonology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
  • 4 Department of Medical Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands; Department of Pharmacy, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Abstract

Multiple small-molecule kinase inhibitors with specific molecular targets have recently been developed for the treatment of Cancer. This article reports the development and validation of an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method to simultaneously analyse the small-molecule kinase inhibitors dacomitinib, ceritinib, lorlatinib, and nintedanib in human plasma. For chromatographic analyte separation, an Acquity UPLC® BEH C18 column 1.7 μm, 50 mm x 2.1 mm was used with a binary gradient of pure water/formic acid/ammonium formate (100:0.1:0.02, v/v/v) and methanol/formic acid (100:0.1, v/v). Calibration curves for all small-molecule kinase inhibitors were 5.00-500 ng/mL. Validation of this method met all requirements of the Food and Drug administration. Additionally, clinical applicability was demonstrated by quantification of multiple samples from a pharmacokinetic study in patients with lung Cancer.

Keywords

Ceritinib; Dacomitinib; Lorlatinib; Nintedanib; Small-molecule kinase inhibitor (SMKI); Ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

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