Eco-Conscious Chromatographic Determination of Anti-depressant Free-Dose Combination in the Presence of Related Impurities.

Abstract

According to the World Health Organization (WHO), a 10% estimate of the pharmaceutical products distributed in developing countries are counterfeit or of a substandard quality, a crucial strategy to help overcome this problem is to develop simple and easily applicable analytical methods for quality control testing of drugs especially those administered in combinations due to their complex nature. Here, we worked towards this goal through the development of a simple, and rapid method based on High Performance Liquid Chromatography coupled with Ultraviolet detection (HPLC-UV) for the simultaneous determination of the anti-depressant free-drug combination consisting of brexpiprazole (BREX) and fluoxetine (FLX) in the presence of fluoxetine related impurities (FLX-A). Chromatographic separation was carried out employing a mixture of 45% ethanol and 55% aqueous solvent consisting of 0.1% triethylamine, 0.15 M sodium dodecyl sulfate and 0.057 M sodium dihydrogen phosphate adjusted to pH 6 using Orthophosphoric acid, separation was performed using hypersil BDS C18 column at 50 ºC, employing isocratic elution, the flow rate was set at 1.5 mL.min-1, and the UV detection was done at 220 nm. Results of the developed method reflects excellent analytical performance, linearity was fulfilled over a concentration range of 5-80 µg.mL-1 for both drugs with correlation coefficients of 0.9996 and 0.9998 for BREX and FLX respectively. The respective values for LOQ and LODs were found to be 2.70, 4.41 µg.mL-1, 0.83 and 1.46 µg.mL-1 for BREX and FLX, in addition, the developed method was utilized to test the purity of both drugs in pharmaceutical formulations through monitoring fluoxetine related impurity. The developed method was also determined to be eco-friendly, as testing with four available assessment tools demonstrated its superior greenness represented by an AGREE score of 0.83.