Forced degradation study of abacavir sulfate under the frame of genotoxic impurity

213-219<span style="font-size: 9.0pt;mso-bidi-font-size:8.0pt" lang="EN-US">Genotoxic impurities in drug substances or drug products are growing concern to ensure public health. Genotoxic impurities present in drug substances and drug products may be DNA reactive and can pose significant problems for drug regulators and industry alike over several decades. The principal concern related to drug safety is the prolong exposure to compounds that can alter DNA, and may ultimately produce carcinogenicity. Therefore, the practical issue to be addressed is that conventional procedures should be available to identify DNA-reactive impurities in the shelf life of drug product. In the present study, abacavir sulfate, an antiretroviral agent is used to evaluate degradation pathways under different stress conditions in order to identify degradation products as prescribed by ICH guidelines. Abacavir sulfate is found to degrade under acidic and oxidative conditions followed by formation of three degradation products which are separated by an isocratic HPLC method. The degradation products are identified by LC-MS to propose degradation pathways followed by evaluation of similarity with the structural alerts for genotoxic impurities. Finally, characterization of the genotoxic impurity can be achieved by FT-IR, NMR and LC-MS. Abacavir sulfate is found to be stable to base hydrolysis and thermal treatment while susceptible to degradation in oxidative stress and acidic hydrolysis. LC-MS study results reveal that possible degradants are C8H10N6 (m/z 191.2) in acidic conditions whereas C14H18N6O3 (m/z 319.2) and C11H14N6O (m/z 247.2) in oxidative stress conditions. Structural alerts for pharmaceutical impurities indicates the formations of N-hydroxyaryls and aza-aryl N-oxides which may be genotoxic impurities. </span

Green synthesis of silver nanoparticles using Ocimum sanctum Linn. and its antibacterial activity against multidrug resistant Acinetobacter baumannii

The biosynthesis of nanoparticles using the green route is an effective strategy in nanotechnology that provides a cost-effective and environmentally friendly alternative to physical and chemical methods. This study aims to prepare an aqueous extract of Ocimum sanctum (O. sanctum)-based silver nanoparticles (AgNPs) through the green route and test their antibacterial activity. The biosynthesized silver nanoparticles were characterised by colour change, UV spectrometric analysis, FTIR, and particle shape and size morphology by SEM and TEM images. The nanoparticles are almost spherical to oval or rod-shaped with smooth surfaces and have a mean particle size in the range of 55 nm with a zeta potential of −2.7 mV. The antibacterial activities of AgNPs evaluated against clinically isolated multidrug-resistant Acinetobacter baumannii (A. baumannii) showed that the AgNPs from O. sanctum are effective in inhibiting A. baumannii growth with a zone of inhibition of 15 mm in the agar well diffusion method and MIC and MBC of 32 µg/mL and 64 µg/mL, respectively. The SEM images of A. baumannii treated with AgNPs revealed damage and rupture in bacterial cells. The time-killing assay by spectrophotometry revealed the time- and dose-dependent killing action of AgNPs against A. baumannii, and the assay at various concentrations and time intervals indicated a statistically significant result in comparison with the positive control colistin at 2 µg/mL (P < 0.05). The cytotoxicity test using the MTT assay protocol showed that prepared nanoparticles of O. sanctum are less toxic against human cell A549. This study opens up a ray of hope to explore the further research in this area and to improve the antimicrobial activities against multidrug resistant bacteria