Simultaneous Quantification of Lamivudine, Tenofovir Disoproxil Fumarate and Doravirine in Pharmaceutical Dosage Form by
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Pharmaceutical Chemistry Journal, Vol. 54, No. 5, August, 2020 (Russian Original Vol. 54, No. 5, May, 2020)
SIMULTANEOUS QUANTIFICATION OF LAMIVUDINE, TENOFOVIR DISOPROXIL FUMARATE AND DORAVIRINE IN PHARMACEUTICAL DOSAGE FORM BY LIQUID CHROMATOGRAPHY WITH DIODE ARRAY DETECTION Gowri Gollu1,* and Sowjanya Gummadi2 Original article submitted March 27, 2020. A new simple, precise and robust isocratic reverse-phase high performance liquid chromatography (RP-HPLC) method was developed and validated for simultaneous determination of lamivudine, tenofovir disoproxil fumarate (TDF), and doravirine in bulk and pharmaceutical dosage form. The validation included specificity, linearity, system suitability, precision, robustness, LOD and LOQ characteristics. The chromatographic separation was achieved on C18 X bridge phenyl column (150 ´ 4.6 mm, 3 mm particle size) eluted with acetonitrile and hexane-1-sulfonic acid (pH 2.5; 50:50, v/v) at a flow rate of 0.8 mL/min and monitored at 243 nm over a run time of 12 min. The retention times of lamivudine, TDF, and doravirine were found to be 2.45, 7.3, and 8.79 min. respectively. The method was linear in the range of 5 – 100 mg/mL (r2 = 0.999) for lamivudine and TDF and in the range of 1.75 – 35 mg/mL (r2 = 0.999) for doravirine. The percentage recoveries of three drugs were within the acceptable limits (98 – 102%). The method was found to be precise as confirmed by % RSD < 0.6. Forced degradation study was conducted as per ICH guidelines, and the three drugs showed degradation within 21.4 – 33.8% under acidic, basic, oxidative, photolysis, and hydrolysis conditions. The proposed RP-HPLC method can be used for the quantification of lamivudine, TDF, and doravirine in API and tablets without any interference from excipients. Keywords: RP-HPLC, doravirine, lamivudine, tenofovir disoproxil fumarate, ICH guidelines, forced degradation.
[[(isopropoxycarbonyl)oxy]methoxy]propyl] adenine fumarate (Fig. 1b ). It exhibits its activity by terminating viral DNA chain elongation, acting an adenosine 5¢-monophosphate analogue. TDF inhibits the activity of viral DNA polymerase and terminates DNA chain elongation by competing with natural substance [3]. Doravirine chemically is 3-chloro-5-({1-[(5-hydroxy-4-methyl-4H-1,2,4-triazol-3-yl) methyl]-2-oxo-4-(trifluoromethyl)-1,2-dihydropyridin-3-yl} oxy) benzonitrile (Fig. 1c ). Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor used to treat HIV infections in adult patients with no prior antiretroviral treatment history. Doravirine shows its activity by inhibiting viral replication through non-competitive inhibition of HIV-1 reverse transcriptase [4]. Varieties of methods are in use for the estimation of TDF as single entity [5, 6] and lamivudine as a single component [7 – 9] in dosage forms and biological samples. Several methods have also been reported for the combination of TDF and lamivudine along with other drugs [10 – 14] in a variety of matrices. However, no methods have been reported till
1. INTRODUCTION Lamivudine is a
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