Quantification of afatinib, alectinib, crizotinib and osimertinib in human plasma by liquid chromatography/triple-quadrupole mass spectrometry; focusing on the stability of osimertinib

Geel

Beer

et al. 2020

A new method for quantification of osimertinib (OSIM) in human plasma using a high‐performance liquid chromatography–tandem mass spectrometry method was developed and validated. Methanol was used for protein precipitation and pazopanib as internal standard. Separation was performed on a HyPURITY®C18 analytical column (50 × 2.1 mm; 3 μm) using a gradient elution of ammonium acetate in water and ammonium acetate in methanol, both acidified with formic acid 0.1%. Detection and quantification of OSIM and pazopanib was performed using a triple quadruple mass spectrometer after electrospray ionization. This method led to robust results, as the selectivity, carryover, precision and accuracy all met pre‐specified requirements. OSIM was stable in human serum when stored at −80°C. Reduced stability was found when stored at 2–4°C or room temperature. Degradation of OSIM slowed down in EDTA–plasma and acidified human serum. The limited stability of OSIM at room temperature should be considered for transport and sample preparation. Plasma samples should be frozen as soon as possible and sample preparation should be performed on dry‐ice. In the future, EDTA–plasma and sample acidification may be used to improve OSIM stability at room temperature. However, more research and validation of such an approach are required.

Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Validation of an analytical method using HPLC–MS/MS to quantify osimertinib in human plasma and supplementary stability results

Geel

Beer

et al. 2020

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

Geel

Schoufs

et al. 2021

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 ® 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 C) and for at least 1 month in EDTA plasma when stored at À80 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.

Development and validation of an HPLC–MS/MS method to simultaneously quantify brigatinib, lorlatinib, pralsetinib and selpercatinib in human K2‐EDTA plasma

Gulikers

Sinkiewicz

et al. 2023

A liquid chromatography-tandem mass spectrometry method was developed and validated to quantify the small-molecule inhibitors (SMIs) brigatinib, lorlatinib, pralsetinib and selpercatinib, which are used in patients with oncogenic-driven non-small cell lung cancer. Chromatographic separation was performed on a HyPURITY ® C 18 analytical column with a gradient elution using 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. The assay was validated over a linear range of 50-2,500 ng/ml for brigatinib, 25-1,000 ng/ml for lorlatinib, 100-10,000 ng/ml for pralsetinib and 50-5,-000 ng/ml for selpercatinib. All four SMIs were stable for at least 7 days under cool conditions (2-8 C), and at least 24 h at room temperature (15-25 C) in K2-EDTA plasma. Under freezing conditions (À20 C), all SMIs were stable for at least 30 days, except for the lowest quality control (QC LOW ) of pralsetinib. The QC LOW of pralsetinib was stable for at least 7 days at À20 C. This method provides an efficient and simple way to quantify four SMIs with a single assay in clinical practice.