HPLC-DAD-CAD-based approach for the simultaneous analysis of hydrophobic drugs and lipid compounds in liposomes and for cyclodextrin/drug inclusion complexes

Abstract

In recent decades liposomes have become attractive carriers for hydrophobic drugs to enhance their solubility and improve their therapeutic application. For liposomal drug products, both drug and lipid quantification are required by regulatory authorities, making the implementation of precise quantification methods a step of crucial importance in formulation development and quality control. Therefore, the present study is focused on the development and validation of a simple and time-saving method for the simultaneous analysis of hydrophobic drugs and conventional liposomal components. The new HPLC method was established with a combined detection by a diode array detector (DAD) and a corona charged aerosol detector (CAD). As a wide calibration range of the liposomal components can be achieved (10−1000 μg/mL), the analysis of samples with different drug to lipid ratios is enabled. Moreover, an excellent precision including repeatability and low limits of detection (≤ 1.8 μg/mL) and limits of quantification (≤ 5.9 μg/mL) were accomplished for all analytes. The method was successfully applied to liposomes incorporating mitotane. Everolimus was additionally analyzed as hydrophobic model drug. Furthermore, cyclodextrin/mitotane inclusion complexes were investigated to proof a broad range of applications for the developed method.