Bortezomib (BTZ), as a proteasome inhibitor, has been used for treatment of patients with relapsed/refractory multiple myeloma and mantle cell lymphoma. BTZ is available for intravenous injection or subcutaneous administration. In this study, for evaluating the potential of BTZ oral delivery, intestinal permeability of BTZ was determined using in situ single-pass intestinal perfusion (SPIP) technique and the perfused solutions were analyzed using a validated HPLC-UV method. The chromatographic separation was performed using a C18 column via isocratic mode at a flow rate of 0.5 mL/min at 270 nm. The mobile phase was a mixture of methanol/deionized water (50:50% v/v) with 0.1% glacial acetic acid. The results indicated that calibration curves were linear (r2 ˃0.99) in a concentration range of 1.65-5 µg/mL for BTZ and 8.33-25 µg/mL for phenol red. A limit of quantitation of 1.03 and 6.67 µg/mL was obtained for BTZ and phenol red, respectively. The recovery values were in the range of 96.5-105.4% for BTZ, and 88-99.2% for phenol red. The relative standard deviations (RSD) were ≤4.9% for BTZ and ≤7% for phenol red. Stability studies indicated that the working standard solution is stable over a period of 48 h at room temperature. Finally, an effective permeability (Peff) value of (3.36±0.5)×10-5 cm/sec (mean±SEM) was achieved for BTZ. Moreover, it was predicted that BTZ belongs to the biopharmaceutical class ІІІ.
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