Quantification of oxaliplatin and lansoprazole in tumor tissue homogenates by LC-MS/MS: a fit-for-purpose bioanalytical approach.

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.