BACKGROUND: Quantification of drug concentrations within tumor tissue is essential for evaluating true intratumoral exposure, yet remains analytically challenging due to matrix complexity, protein binding, and drug instability. Existing LC-MS/MS methods for oxaliplatin and lansoprazole are primarily limited to plasma or pharmaceutical matrices. METHODS: This study describes the development and fit-for-purpose evaluation, guided by ICH M10 principles, of LC-MS/MS methods for quantifying oxaliplatin and lansoprazole in murine tumor tissue homogenates. Isocratic separation on a C18 column with an ammonium acetate-acetonitrile mobile phase and compound-specific MRM detection enabled selective analysis. RESULTS: The methods demonstrated acceptable linearity, agreement between nominal and back-calculated concentrations, controlled matrix effects, consistent extraction recovery, and satisfactory autosampler and freeze-thaw stability. The assays were successfully applied to determine intratumoral drug concentrations in control, monotherapy, and combination treatment groups. CONCLUSION: These matrix-matched LC-MS/MS methods provide a fit-for-purpose approach for exploratory intratumoral drug quantification and support more reliable assessment of pharmacologically relevant tumor exposure in preclinical studies.
Alves et al. (Fri,) studied this question.