Development and validation of an HPLC-MS/MS method to simultaneously quantify alectinib, crizotinib, erlotinib, gefitinib and osimertinib in human plasma samples, using one assay run

A. van Veelen, R. van Geel, R. Schoufs, Y. de Beer, L.M. Stolk, L.E.L. Hendriks, S. Croes*

*Corresponding author for this work

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Abstract

A liquid chromatography-tandem mass spectrometry method was developed and validated to quantify alectinib, crizotinib, erlotinib and gefitinib. This assay can be combined with our method for osimertinib, allowing quantification of the most used ALK- and EGFR-tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer with a single-assay setup. Chromatographic separation was performed on a HyPurity (R) C-18 analytical column using an elution gradient of ammonium acetate in water and in methanol, both acidified with formic acid 0.1%. Detection and quantification were performed using a triple quad mass spectrometer with an electrospray ionization interface. This method led to robust results, as the selectivity, carryover, precision and accuracy met all pre-specified requirements. The assay was validated over a linear range of 100-2,000 ng/ml for alectinib and erlotinib and 50-1,000 ng/ml for crizotinib and gefitinib. Alectinib, crizotinib, erlotinib and gefitinib were all stable for at least 4 h in whole blood (at room temperature and at 4 degrees C) and for at least 1 month in EDTA plasma when stored at -80 degrees C, while osimertinib proved to be unstable at room temperature. Although high-performance liquid chromatography was used, the run time was short and comparable with other methods using ultra-high performance liquid chromatography.
Original languageEnglish
Article numbere5224
Number of pages13
JournalBiomedical Chromatography
Volume35
Issue number12
Early online date31 Aug 2021
DOIs
Publication statusPublished - Dec 2021

Keywords

  • LC-MS
  • MS analysis
  • non-small cell lung cancer
  • tyrosine kinase inhibitors
  • validation
  • CELL LUNG-CANCER
  • OPEN-LABEL
  • RAPID-DETERMINATION
  • 1ST-LINE TREATMENT
  • MASS-SPECTROMETRY
  • KINASE INHIBITORS
  • CHEMOTHERAPY
  • AFATINIB

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