Two simple and selective methods were developed for the simultaneous determination of tenofovir fumarate (TEN) and emtricitabine (EMT) in combined tablets. The first method involves the application of first derivative spectrophotometry where the first derivative amplitudes were measured at 298.5？nm for determination of EMT in presence of TEN. The second method involves first derivative of ratio spectra spectrophotometry where the amplitudes at 251.5？nm have been used for quantitation of TEN in the presence of EMT. Different variables affecting each method were carefully investigated and optimized. Reliability and analytical performance of the proposed methods, including linearity, range, precision, accuracy, detection, and quantitation limits, were statistically validated. The methods were successfully applied for the determination of EMT and TEN in laboratory-prepared mixtures and in their combined tablets. 1. Introduction Antiviral drugs development has become a very active area in the last decade, especially with the challenges of AIDS, hepatitis, and avian and swine flu epidemics. The antiviral drugs are used in the treatment of viral infections. They may also be used to provide protection, usually for a brief period only, against infection. There is little evidence that these compounds affect latent or nonreplicating virus. Nonspecific symptomatic and supportive treatment is also important in the management of viral infections. Tenofovir disoproxil fumarate (TEN) is 9-[(R)-2 [[bis[[(isopropoxycarbonyl)oxy]methoxy] phosphinyl] methoxy] propyl] adenine fumarate [1] (Figure 1). It belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people [2, 3]. Figure 1: Structures of tenofovir disoproxil fumarate (TEN) and emtricitabine (EMT). Emtricitabine (EMT), 4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-1,2-dihydropyrimidin-2-one [1] (Figure 1), works by inhibiting reverse transcriptase enzyme that copies HIV RNA into new viral DNA. It can help lower the level of HIV in the patient’s body and can indirectly increase the number of immune system cells. EMT is indicated in combination with other antiretroviral agents for the treatment of HIV and HBV infection in adults [2, 3]. Being relatively recent drugs, TEN and EMT are not official in BP 2010 or USP 2011. TEN is formulated in binary mixture with the reverse transcriptase inhibitor emtricitabine (EMT) to prevent HIV from altering the
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