Two simple, rapid, sensitive, accurate, precise and economical Visible Spectrophotometric methods have been developed for the determination of Etravirine in pure and pharmaceutical formulations. These methods (A and B) were based on nucleophilic substitution and oxidative coupling reactions of Etravirine by 1,2-naphtha quinone-4-sulphonate (NQS) in alkaline medium and 3-methyl-2-benzothiazolinone hydrazone (MBTH) in acidic medium with the maximum absorbance at 414 nm and 635 nm respectively. Linearity was obtained in the concentration range of 5 -30 μg/ml and 2 -10 μg/ml which was corroborated by the correlation coefficient (r) values of 0.9995 and 0.9996 respectively. The methods developed were validated with respect to linearity, accuracy (recovery), precision, Sandell’s sensitivity, molar extinction coefficient and specificity. The proposed methods are successfully applied for the determination of Etravirine in bulk and pharmaceutical formulations and results were validated statistically by recovery studies.
A novel stability indicating reverse phase ultra performance liquid chromatographic (UP-LC) method has been developed for Etravirine along with eight impurities (imp-1, imp-2, imp-3, imp-4, imp-5, imp-6, imp-7 and imp-8) and validated as per ICH recommendations. Stress degradation conditions were established for Etravirine by subjecting it to stress conditions of acid, base, oxidation, humidity, thermal and photolysis. Significant degradation is observed in base stress condition and the major degradant (RRT at about 0.94) is identified by LC-MS and spectral analysis. The stress samples were assayed against a qualified reference standard and the mass balance was found close to 99.0%. Efficient chromatographic separation was achieved on a Shimpack ODS-II stationary phase with a gradient mobile phase combination. Quantification was carried at 303 nm at a flow rate of 0.6 mL?min–1. The resolution between Etravirine and eight potential impurities is found to be greater than 2.0. Regression analysis shows as r value (correlation coefficient) of greater than 0.999 for Etravirine and eight potential impurities. This method is capable to detect the impurities of Etravirine at a level of 0.003% with respect to test concentration of 1.0 mg·mL–1.
Mohanareddy ChilukuriKatreddi H. ReddyPapadasu NarayanareddyMadireddi Venkataramana
Objectives: The aims of this study was to analyze the immuno-virologic response after optimised background antiretroviral therapy (OBT) associated to new active antiretroviral treatment (ART) in HIV-1 infected patients with chronic virologic failure. Methods: We conducted a descriptive analysis of the immuno-virologic responses in HIV-1 adult infected patients: 1) harbouring multiple therapeutic failures with ART;2) with no virologic response obtained over 10 years (1997-2008);and 3) treated with OBT combined with new drugs including at least 1 of the 3 active ART among darunavir/ritonavir, etravirine and raltegravir;4) observed between month 0 (M0), before new ART to month 12 (M12) after new ART initialisation. Results: Twenty three patients were included in the study. After OBT, the proportion of patients with undetectable viral load was significantly higher at M6 and M12 than M0 (86% and 73% versus 0%, p = 0.03, respectively). At the same period, the median HIV viral load decreased significantly in 19/23 (83%) patients from 4.3 to 1.69log10 HIV-1 RNA copies/ml (p 3 [0 - 604] to 449/mm3 [130 - 964] between M0 and M12 (p 3 decreased from 57% to 23% (p = 0.02). Tolerability was good and no death was recorded during the 12-month' follow-up. Conclusions: These results show that the combination of OBT with the new ART can offer a salvage therapy in patients presenting a long-term history of virologic failures.
Vincent GuiyediOlivier MounourySoraya BoucheritPascale LonguetCBrunet-FrancoisEric KendjoJLEcobichonMadeleine Okome-NkoumouCatherine LeportFRaffi
