3 years ago

Development and validation of a UPLC‐MS/MS method for quantification of osimertinib (AZD9291) and its metabolite AZ5104 in human plasma

Yanbao Zhang, Xin Zheng, Yuxiang Ma, Pei Hu, Ji Jiang, Hongyun Zhao, Weicong Wang


Osimertinib (AZD9291) is a highly selective irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) designed to treat non‐small cell lung cancer (NSCLC) patients with EGFR active and T790M resistant mutations. A rapid and sensitive method for quantitative analysis by ultra‐performance liquid chromatography‐tandem mass spectrometry (UPLC‐MS/MS) of osimertinib and its metabolite AZ5104 in human plasma was developed and validated. The samples were prepared by protein precipitation (PP) and separated on a BEH C18 column (2.1×50 mm, 1.7 μm) by gradient elution with 0.1% (v/v) formic acid and 10 mM ammonium acetate in water and acetonitrile as the mobile phase. Electrospray ionization (ESI) in positive ion mode and multiple reaction monitoring (MRM) were used to monitor the ion transitions at m/z 500.4→385.3 and 486.3→371.1. The results indicated that the method had excellent sensitivity and specificity. The validation was performed in a range from 0.5 to 100 ng/mL. Intra‐day and inter‐day precisions (in terms of % RSD) were all <15%, and the accuracies (in terms of % RE) were within the range of ±15%. The lower limit of quantification (LLOQ), matrix effect, extraction recovery, stability and dilution integrity were also validated and satisfied with the validation criteria. Finally, this method was successfully applied in a retrospective analysis, and the predose samples of 52 NSCLC patients who were enrolled in a novel 3rd EGFR TKI clinical trial were analyzed for screening regardless of whether they had previously received osimertinib treatments.

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