A fast method for the quantification of bortezomib in serum and rat nervous tissue by liquid chromatography tandem mass spectrometry

Bortezomib is a proteasome inhibitor used to treat cancers such as Multiple Myeloma and Mantle Cell Lymphoma. Due to its narrow therapeutic index, accurate quantification in biological matrices is essential for monitoring drug exposure, optimizing dosing, and assessing tissue distribution. The aim of this study was to develop and validate LC-MS/MS methods for the quantification of bortezomib in rat serum and rat sciatic nervous tissue. A rapid serum assay based on one-step protein precipitation and a nervous tissue assay were established using 2 H 8 -Bortezomib as an isotope labeled internal standard. Calibration ranges were 0.920–100 ng/mL for serum and 4.00–100 ng/g for nervous tissue. Bortezomib and its internal standard were detected using high-resolution MRM in positive-mode electrospray ionization, with a total acquisition time of 4 min per run. The serum method was validated according to ICH M10 guideline, ensuring compliance with parameters including accuracy, precision, matrix effects, recovery, stability, selectivity, reinjection reproducibility, and carry-over. The nervous tissue method underwent partial validation, assessing key parameters to ensure reliable quantification. The application of these methods to authentic rat samples demonstrated their suitability. The developed assays provide rapid and sensitive quantification of bortezomib in serum and sciatic nervous tissue. The simple sample preparation procedures and short run times support their use in pharmacokinetic and tissue distribution studies.