Simultaneous quantitation of befotertinib (D-0316) and its metabolite D-0865 in human plasma by LC-MS/MS method.

A sensitive and reliable method was developed to determine befotertinib (D-0316) and its metabolite D-0865 from human plasma by LC-MS/MS. The samples were prepared by simple protein precipitation and 2 µL of the supernatant were chromatographed on a C18 analytical column (ACE Excel 2 Super C ₁₈ , 50 × 2.1 mm). Elution was performed with mobile phase A (10 mM ammonium acetate in water containing 1 % formic acid) and mobile phase B (acetonitrile containing 1 % formic acid) under a gradient program in a total run time of 4 min. Triple Quadruple 5500 equipped with Turbo Ion Spray source and multiple reaction monitoring (MRM) were used for the analysis detection. The transitions were m/z 568.3 → 72.1 m/z (befotertinib), m/z 554.2 → 497.2 (D-0865), and m/z 455.2 → 164.9 (verapamil, internal standard). According to the Chinese Pharmacopeia Commission and ICH Harmonised Guideline for Bioanalytical Method Validation, this method was validated within the spectrum of its accuracy, precision, selectivity, linearity, recovery, matrix effect, and stability. This LC-MS/MS method was successfully applied for the quantitation of befotertinib and its metabolite D-0865 in human plasma during the pharmacokinetics study of befotertinib in non-small cell lung cancer (NSCLC) patients.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lieming Ding reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment and equity or stocks. Hua Li reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Yang Wang reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Ru Ding reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Chen Chen reports a relationship with Betta Pharmaceuticals Co ltd that includes: employment. Zhixuan Tian reports a relationship with Suzhou Sanclinty Co., ltd that includes: employment. Hongnan Yin reports a relationship with Suzhou Sanclinty Co., ltd that includes: employment.].
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