FORCED DEGRADATION STUDY OF DARUNAVIR ETHANOLATE AND RITONAVIR COMBINATION IN ACIDIC, BASIC AND OXIDATIVE CONDITIONS ESTABLISHING DEGRADATION PRODUCTSAbstract
A simple, precise, and rapid stability indicating RP-HPLC method has been developed for the simultaneous estimation of darunavir ethanolate and Ritonavir in Pharmaceutical dosage form in the presence of degradation products. It involved the Zorbax bonus, 150 mm × 4.6 mm of 3.5 μm particles packing stationary phase. The separation was achieved using mobile phase a consists of ammonium acetate buffer: methanol; 50:50 (% v/v) mixture and mobile phase B consists of ammonium acetate buffer: acetonitrile; 45:55 (% v/v) mixture with the flow rate of 1.0 ml/min, gradient program was applied from 0.0 min to 35.0 min. The effluent is monitored at 240 nm. The retention time of darunavir ethanolate and ritonavir was found to be 7.39 ± 0.09 min and 16.18 ± 0.007 min, respectively, with a total run time of 35 min. Forced degradation study was carried out in acid, base, and oxidative conditions where 3 degradation products; DP1, DP2, and DP3 were observed in acidic condition at RT 1.765 min, 4.276 min, 8.261 min, and 4 degradation products; DP4, DP5, DP6, and DP7 were observed in basic condition at RT 1.789 min, 4.858 min, 7.518 min, and 13.179 min. However, no degradation products were visually observed in oxidative conditions. The method was found to be specific enough to separate degradation products from main analytes. The method was linear in the range of 240-560 μg/ml (R²=0.999) and 30-70 μg/ml (R²=0.999) for darunavir ethanolate and ritonavir, respectively. The described method was validated and result of each parameter was met with its acceptance criteria.
A. A. Bana, P. Patel and P. J. Mehta *
Department of Pharmaceutical Analysis, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat, India.
08 November 2019
05 May 2020
17 June 2020
01 November 2020