A new stability indicating RP-UPLC method for simultaneous estimation of Doravirine, Lamivudine and Tenofovir disoproxil fumarate in bulk and their combined pharmaceutical formulation

Abstract

Background To establish a simple, sensitive, accurate, precise, efficient, economical RP-UPLC method for simultaneous estimation of Doravirine, Lamivudine and Tenofovir disoproxil fumarate in bulk and their combined pharmaceutical formulations. Optimization of Chromatographic separation was achieved on analytical column HSS C18 (100 × 2.1 mm, 1.8 μ) maintained at temperature 30 °C and mobile phase consisting of 0.01 N Potassium dihydrogen orthophosphate buffer (pH-4.8) and acetonitrile in the ratio 60:40 v/v and at a flow rate 0.3 mL/min in isocratic mode. The injection volume was set as 1 µl detection wavelength is 260 nm. The proposed method validation was done as per International Council on Harmonization Q2 (R1) guidelines. Results Doravirine, Lamivudine and Tenofovir disoproxil fumarate were eluted at retention times of 1.2, 1.5, and 1.8 min respectively. The proposed method was identified an excellent linearity over concentration range of 12.5–75.0 µg/mL for Doravirine and 37.5–225.0 µg/mL for Lamivudine and 37.5–225.0 µg/mL for Tenofovir disoproxil fumarate. The percentage relative standard deviation for intra-day and inter-day precision of the present method was less than 2% for Doravirine, Lamivudine and Tenofovir disoproxil fumarate. Accuracy of the present method was evaluated by recovery studies which were in the range of 99.62–99.88% for Doravirine and 98.78–99.44% for Lamivudine and 99.67–100.52% for Tenofovir disoproxil fumarate. The limit of detection and limit of quantification were found to be 0.249 µg/mL and 0.756 µg/mL for Doravirine and 0.24 µg/mL and 0.727 µg/mL for Lamivudine and 0.797 µg/mL and 2.966 µg/mL for Tenofovir disoproxil fumarate. Forced degradation studies were carried out under various stress conditions like acid, base, peroxide, thermal, photo and neutral conditions. Conclusions The present method makes sure about no degraded impurity peak interference at the retention time of analyte peak hence can be applied for quality control investigation of Doravirine, Lamivudine and Tenofovir disoproxil fumarate in bulk and pharmaceutical formulations.

Overview of Forced Degradation Analysis for FDA Approved Antiretroviral agents: A Review

“…Antiviral medicines have been quantified using a variety of methods, including UV, capillary electrophoresis, and chromatographic methods such as GC and HPLC, LC-MS, and GC-MS. The authors of this review focus on stability, recommending HPLC/RP-HPLC technologies for the precise and effective development and validation of antiviral medicines such as Zidovudine, [15][16][17][18][19][20] Lamivudine, [20][21][22][23] Nevirapine, [24][25][26][27] Ritonavir, [28][29][30][31] Abacavir, [32][33][34] Efavirenz, [35][36][37][38] Tenofovir, [39][40][41] Fosamprenavir, [42][43][44][45][46] Atazanavir, [47][48] Emtricitabine, 35,35,39,49 Fosamprenavir, [42][43][44][45][46] Tipranavir, [50][51] Darunavir, [52]…”

Analytical Review on Newly Approved Antidiabetic and Antihypertensive Drugs

“…74 The stability-indicating RP-UPLC method. 75 and LC-MS/MS 76 were created to simultaneously determine the concentrations of both sitagliptin and ertugliflozin.…”

Untitled

“…Vasantha K and Rao GD: Stability indicating RP-HPLC method for estimation of doravirine, lamivudine and tenofovir disoproxil fumarate in pharmaceutical dosage form. Int J Pharm Sci & Res 2022; 13(9): 3737-48. doi: 10.13040/IJPSR.0975-8232.13 (9).3737-48.…”

“…The chemical name for DOR is 3-chloro-5-[[1-[(4,5dihydro -4methyl -5oxo -1H-1, 2, 4 -triazol-3-yl)methyl]-1,2-dihydro-2-oxo-4(trifluoromethyl)-3-pyridinyl] oxy] benzonitrile. Hinging on the literature, only a few methods were established to estimate Doravirine, Lamivudine and Tenofovir Disoproxil Fumarate by HPLC-DAD 8 , UPLC 9 in plasma samples 10 . Accordingly, the present research aimed to develop a cost-efficient, specific and precise method for the determination of Doravirine, Lamivudine and Tenofovir Disoproxil Fumarate in its marketed tablet dosage form.…”