A STABILITY-INDICATING HPLC METHOD FOR THE DETERMINATION OF POTENTIAL IMPURITIES IN A NEW FIXED DOSE COMBINATION OF DOLUTEGRAVIR, LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS USED IN THE FIRST LINE TREATMENT OF HIV-1 INFECTION

Abstract

Developing a single method for the quantification of related compounds for a combination product containing three active ingredients is difficult task. Separation and compromising run time to elute all known and unknown degradation products are crucial for a combination product. The aim of current work is to develop a new stability indicative method and validate for a fixed dose combination product containing dolutegravir, lamivudine, tenofovir disoproxil fumarate and their potential impurities in a single run by HPLC. The critical separation between dolutegravir, lamivudine, tenofovir disoproxil fumarate and its impurities was successfully attained by a new core-shell bi-phenyl, 250x4.6mm, 5µm column with a run time of 150 min. The run time was 150min. Forced degradation studies were verified to prove the stability-indicating nature of the method. Stability-indicating nature was confirmed by peak purity of all the three active components and impurities. The developed method was validated to prove the potentiality of the method as per ICH guidelines with respect to specificity, linearity, accuracy, precision ad robustness. The sensitivity of the method was proved by establishing limit of detection (LOD) and limit of quantification (LOQ) of for dolutegravir, lamivudine, tenofovir disoproxil fumarate and potential impurities.