Box‐Behnken assisted development and validation of high‐performance liquid chromatography method for the simultaneous determination of doxorubicin and vorinostat in polymeric nanoparticles

Abstract

While histone deacetylase inhibitors, such as vorinostat, demonstrate a significant effect against hematological cancers, their application for solid tumor treatment is limited. However, there is strong evidence that combinatorial administration of vorinostat and genotoxic agents (e.g., doxorubicin) enhances the antitumoral action of both drugs against tumors. We developed a high‐performance liquid chromatography method for the 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:ACN (90:10 v/v) as mobile phase at 240 nm. The 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 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 the 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.

White analytical chemistry‐driven stability‐indicating concomitant chromatographic estimation of thiocolchicoside and aceclofenac using response surface analysis and red, green, and blue model

“…In recent years, numerous AQbD‐based chromatographic methods have been reported in the literature for the analysis of drugs. Hence, the AQbD‐based chromatographic method is the best alternative to support concepts of WAC and green analytical chemistry [5–27].…”

Green analytical chemistry‐driven response surface modeling to stability‐indicating chromatographic method for estimation of cilnidipine and application of high‐performance thin‐layer chromatography–mass spectrometry for characterization of degradation products

“…Numerous research papers in the literature have described the chromatographic analysis of pharmaceutical substances and products by RP-HPLC and HPTLC using the design of experiments (DoE)-based AQbD approach [4][5][6][7][8][9][10][11][12][13][14]. Recently, some green analytical chemistry and white analytical chemistry-based method development reports have been published in the literature [15][16][17].…”