Jump to main content
Jump to site search

Issue 9, 2019, Issue in Progress
Previous Article Next Article

A simple liquid chromatography-tandem mass spectrometry method to accurately determine the novel third-generation EGFR-TKI naquotinib with its applicability to metabolic stability assessment

Author affiliations

Abstract

Naquotinib (ASP8273, NQT) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs). NQT was found to be more effective than osimertinib against the EGFR L858R plus T790M mutation (L858R+T790M). A rapid resolution liquid chromatography (RRLC)-tandem mass spectrometry (MS/MS) method was developed and validated for NQT quantification and its metabolic stability was investigated. NQT and foretinib (FTB) as an internal standard (IS) were separated using a mobile phase under isocratic conditions with a C18 column (reversed phase system). The linearity of the analytical method ranged from 5 to 500 ng mL−1 (coefficient of correlation [r2] ≥ 0.9999) in a human liver microsome (HLM) matrix. The limit of detection and limit of quantification were 0.78 and 2.36 ng mL−1, respectively. The inter-day and intra-day accuracy and precision were −6.36 to 1.88 and 0.99 to 2.58%, respectively. The metabolic stability of NQT in the HLM matrix was calculated using the in vitro half-life (t1/2, 67.96 min) and intrinsic clearance (Clint, 2.12 mL min−1 kg−1). NQT is considered to be a moderate extraction ratio drug that is moderately excreted from the human body compared with other related TKIs. This proposed methodology is thought to be the first method for assessing NQT concentration and its metabolic stability.

Graphical abstract: A simple liquid chromatography-tandem mass spectrometry method to accurately determine the novel third-generation EGFR-TKI naquotinib with its applicability to metabolic stability assessment

Back to tab navigation

Publication details

The article was received on 29 Nov 2018, accepted on 27 Jan 2019 and first published on 07 Feb 2019


Article type: Paper
DOI: 10.1039/C8RA09812C
RSC Adv., 2019,9, 4862-4869
  • Open access: Creative Commons BY license
  •   Request permissions

    A simple liquid chromatography-tandem mass spectrometry method to accurately determine the novel third-generation EGFR-TKI naquotinib with its applicability to metabolic stability assessment

    H. Alrabiah, A. A. Kadi, Mohamed W. Attwa and A. S. Abdelhameed, RSC Adv., 2019, 9, 4862
    DOI: 10.1039/C8RA09812C

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements