A validated liquid chromatography tandem mass spectrometry method for quantification of erlotinib, OSI-420 and didesmethyl erlotinib and semi-quantification of erlotinib metabolites in human plasma
2015 (English)In: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 107, 186-195 p.Article in journal (Refereed) Published
A liquid chromatography tandem mass spectrometry method was developed and validated for quantification of erlotinib and its metabolites in human plasma. The method is suitable for therapeutic drug monitoring and pharmacokinetic studies. The substances were extracted using protein precipitation, separated on a BEH XBridge C18 column (100 x 2.1 mm, 1.7 mu m) by gradient elution at 0.7 mL/min of acetonitrile and 5 mM ammonium acetate. The concentration was determined using a Waters Xevo triple quadrupole mass spectrometer in a multi reaction monitoring mode. The total run time was 7 min. Deuterated erlotinib and OSI-597 were used as internal standard for erlotinib and its metabolites, respectively. Erlotinib, OSI-420 and didesmethyl erlotinib were quantified in the concentration range 25-5000 ng/mL, 0.5-500 ng/mL and 0.15-10 ng/mL, respectively. Precision and accuracy was less than14% except for OSI-420 at LLOQ (17%). Extraction recovery was above 89%, 99% and 89% for erlotinib, OSI-420 and didesmethyl erlotinib, respectively. The human liver microsomes generated 14 metabolites, three of them not previously reported. Twelve metabolites were measured semi-quantitatively and validated with respect to selectivity, precision and stability. (C) 2014 Elsevier B.V. All rights reserved.
Place, publisher, year, edition, pages
Elsevier , 2015. Vol. 107, 186-195 p.
LC-MS/MS; Human liver microsomes; Non-small cell lung cancer; EGFR; Tyrosine kinase inhibitor
IdentifiersURN: urn:nbn:se:liu:diva-117227DOI: 10.1016/j.jpba.2014.12.022ISI: 000351116900024PubMedID: 25594896OAI: oai:DiVA.org:liu-117227DiVA: diva2:807205
Funding Agencies|Swedish Research Council [C0592901, A0671101]; Swedish Cancer Society ; Medical Research Council of Southeast Sweden 2015-04-232015-04-212015-08-06