Development and validation of a rapid UPLC-MS/MS method for quantifying bevacizumab in human plasma and application...

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, is widely used in the treatment of various cancers. Despite its efficacy, the drug exhibits significant interindividual variability in pharmacokinetics and clinical response. This study aimed to develop and validate a rapid, sensitive, and cost-effective ultra-performance liquid chromatography-tandem mass spectrometry method for quantifying bevacizumab in human plasma. Bevacizumab was quantified using the surrogate peptide, FTFSLDTSK. The IgG-based drug, infliximab was used as internal standard. The method was validated for specificity, linearity, precision, accuracy, recovery, matrix effect, stability, and applied in 48 plasma samples from Chinese patients with cancers. The method showed a linear range of 1-200 mg/L, and validation parameters met the required standard criteria. A 14-fold inter-individual variability in bevacizumab trough concentrations (ranging from 10.31 to 143.07 mg/L) was observed, with differences across cancer types. This method provides a simple and rapid approach for bevacizumab quantification and may support individualized dosing strategies.