Box-Behnken assisted development and validation of HPLC method for simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles

While histone deacetylase inhibitors, such as vorinostat, demonstrate significant effect against hematological cancers, its application for solid tumors treatment is limited. However, there is strong evidence that combinatorial administration of vorinostat and genotoxic agents (e.g., doxorubicin) enhance the antitumoral action of both drugs against tumors. We developed HPLC method for simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles designed to provide the parenteral administration of both drugs and increase their safety profile. We performed separation on Nucleodur C-18 Gravity column with a mixture of 10 mM potassium dihydrogen phosphate buffer pH 3.9: acetonitrile (90:10 v/v) as mobile phase at 240 nm. Method was linear within the concentration range of 4.2-52.0 μg/mL for both drugs with limits of detection and quantification of 3.5 and 10.7 μg/mL for doxorubicin and of 2.5 and 7.7 μg/mL for vorinostat, respectively. The method was precise and accurate over the concentration range of analysis. Drug loading was 5.4% for doxorubicin and 0.8% for vorinostat. Degradation of doxorubicin after irradiation was less than 5 %, while amount of vorinostat decreased at 88 % under the same conditions. Thus, the validated method could be adopted for routine simultaneous analysis of doxorubicin and vorinostat in polymeric nanoparticles. This article is protected by copyright. All rights reserved.

Box-Behnken design; doxorubicin; nanoparticles; validation; vorinostat.