Jump to main content
Jump to site search

Issue 70, 2018
Previous Article Next Article

Investigation of the metabolic stability of olmutinib by validated LC-MS/MS: quantification in human plasma

Author affiliations

Abstract

Olmutinib (OTB, Olita™) is an orally available third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI). It was developed by Boehringer Ingelheim and Hanmi Pharmaceutical Co. Ltd for the cure of non-small cell lung cancer (NSCLC). In May 2016, OTB was approved in South Korea for the treatment of patients suffering from metastatic or locally advanced EGFR T790M mutation-positive NSCLC. A LC-MS/MS methodology was validated for OTB quantification in human plasma. An extended application for this validated LC-MS/MS is OTB metabolic stability evaluation. Chromatographic separation of OTB and ponatinib (PNT, IS) was attained using a reversed phase with isocratic elution. The linearity of the developed LC-MS/MS method ranged from 5.00 to 500.00 ng mL−1 with r2 ≥ 0.9999 in human plasma. LOD and LOQ were 1.12 and 3.39 ng mL−1, respectively. The intra-day and inter-day precision and accuracy were 1.17 to 2.75% and 97.86 to 101.48%, respectively. The intrinsic clearance (CLint) was 2.71 mL min−1 kg−1 and the in vitro half-life (t1/2) was 48.80 min. A review of the literature revealed that there are no previous articles about the quantification of OTB in human plasma using LC-MS/MS or its metabolic stability assessment.

Graphical abstract: Investigation of the metabolic stability of olmutinib by validated LC-MS/MS: quantification in human plasma

Back to tab navigation

Publication details

The article was received on 02 Oct 2018, accepted on 15 Nov 2018 and first published on 04 Dec 2018


Article type: Paper
DOI: 10.1039/C8RA08161A
RSC Adv., 2018,8, 40387-40394
  • Open access: Creative Commons BY license
  •   Request permissions

    Investigation of the metabolic stability of olmutinib by validated LC-MS/MS: quantification in human plasma

    Mohamed W. Attwa, A. A. Kadi, H. W. Darwish and A. S. Abdelhameed, RSC Adv., 2018, 8, 40387
    DOI: 10.1039/C8RA08161A

    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