DEVELOPMENT AND VALIDATION OF A NEW RP-HPLC METHOD FOR SIMULTANEOUS DETERMINATION OF ANTIRETROVIRAL DRUGS: COBICISTAT AND ELVITEGRAVIR

A simple, precise, rapid and accurate reverse phase HPLC method was developed for the simultaneous estimation of cobicistat and elvitegravir in the pharmaceutical dosage form. A column of ODS (250mm 4.6mm; i.d and 5μ particle size) was used along with the mobile phase comprising of 0.02M dipotassium hydrogen orthophosphate buffer (pH adjusted to 3.3) and methanol in the ratio of 80:20 (v/v). The flow rate was maintained at 1.0 ml/min and the effluents monitored at 254 nm. The retention time for cobicistat was found to be 2.58 ± 0.3 min and elvitegravir was 3.71 ± 0.3 min. The detection concentration was linear over 125-750 μg/ml for cobicistat and 12.5-75 μg/ml for elvitegravir. Regression equations of cobicistat and elvitegravir were found to be y = 25883x + 19711 and y = 27696x + 6046 respectively with regression co-efficient 0.999. The % RSD for Intra and Inter day precision was < 2%. The accuracy of method was validated by recovery studies and found to be significant within acceptable range 98-102%. The developed method was successfully validated in accordance with ICH guidelines. The present study demonstrates the applicability of chromatographic method to develop a new, sensitive, single RP-HPLC method for the simultaneous quantitative determination of cobicistat and elvitegravir in fixed pharmaceutical dosage form. Hence, this method can be conveniently adopted for routine analysis in quality control laboratories. INTRODUCTION: Cobicistat and Elvitegravir combined dosage form is used for the treatment of HIV infection in adult patients. Cobicistat is chemically as 1,3-thiazol-5-ylmethyl N-[(2R,5R)5-[[(2S)-2-[[methyl [(2propa2-yl-1, 3-thiazol-4-yl) methyl] carbamoyl] amino]-4 morpholin-4-yl butanoyl] amino]-1, 6-diphenylhexan-2-yl] carbamate which acts as an HIV integrase inhibitor 1, 2 . QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.10(11).4981-87 This article can be accessed online on www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.10(11).4981-87 FIG. 1: CHEMICAL STRUCTURE OF COBICISTAT It has a molecular formula of C40H53N7O5S2 and a molecular weight of 776.0 g/mol Fig. 1. It is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A) isoforms. Cobicistat does not have any anti-HIV activity on its own. It is a new pharmacokinetic enhancer, metabolized by CYP3A and especially used to increase elvitegravir levels when administered.