HPLC-PDA identification and resolution of rufinamide forced degradation impurities: A congregated chemometric expedite optimization coupled with factorials and desirability.

Rufinamide is used presently to treat Lenaux-Gastaut syndrome. A full factorial design and desirability approach was investigated for the optimization of hydrolytic stress via response surface curves (RSCs). The degradation impurities were identified and resolved using reversed-phase high-performance liquid chromatography (RP-HPLC) on the Qualisil® BDS C8 column. Acetonitrile-water (29:71, v/v) was optimized for the mobile phase and used at a flow rate of 1.0 ml/min with detection at a wavelength of 230 nm. Rufinamide showed appreciable susceptibility to hydrolysis under acidic and alkaline stress, and substantial degradation in the neutral condition. It degraded much less under oxidative stress. Exposure towards thermal and photolytic stress conditions indicated appreciable stability. The developed method was subjected to validation as per the recommendations of the International Conference on Harmonization. The proposed method showed no influence from the excipients and the degradation products. As well as good precision and accuracy in determination, the method showed a linear response between 2 and 12 µg ml-1 . The method was extended for determination in a human plasma sample, which resulted in excellent recovery without interference from matrix effects. The combined use of desirability and design for the optimization of acidic and alkaline hydrolytic stress led to simple and rapid analysis.

Pharmaceutical Analytical Profile for Novel SGL-2 Inhibitor: Dapagliflozin.

Dapagliflozin (DPG) is a novel drug from class of sodium glucose co-transporter 2 (SGL-2) inhibitors which has been evolved as profound treatment option for the type-2diabetes mellitus (T2DM). Considering the severity of the disease the drug is of crucial significance for the therapy and associated research. As a pharmaceutical dosage form DPG has immense importance as an individual drug and with other antidiabetic drugs as combinations. The drugs existing in combination with DPG are Metformin (MET) and Saxagliptin (SXG). The existence of the Dapagliflozin in combinations further created more interest in reviewing its pharmaceutical, analytical and bio-analytical profile. Such estimations are always in need of precise pharmacological and physicochemical information; hence authors have presented it beforehand. Authors hereby wish to present an essential update pertaining to emergence of gliflozins and DPG. The article further presents a simultaneous and comparative assessment of the analytical investigations published in literature for pharmaceutical estimation to assist future analysis. The thorough literature searches revealed fifty three research papers in total till date. A comprehensive presentation of typical; hyphenated and unique methods used for analysis are outlined effectively. The percentile utilization of analytical approaches since appearance of first publication in 2010 is investigated to report trend in determination. The present review explores the pharmaceutical estimation of DPG to scientifically potentiate analytical research and therapeutic future of DPG as a novel SGL-2 Inhibitor antidiabetic.

Pharmaceutical analysis combined with in-silico therapeutic and toxicological profiling on zileuton and its impurities to assist in modern drug discovery.

The obligatory testing of drug molecules and their impurities to protect users against toxic compounds seems to provide interesting opportunities for new drug discovery. Impurities, which proved to be non-toxic, may be explored for their own therapeutic potential and thus be a part of future drug discovery. The essential role of pharmaceutical analysis can thus be extended to achieve this purpose. The present study examined these objectives by characterizing the major degradation products of zileuton (ZLT), a 5-lipoxygenase (5-LOX) inhibitor being prevalently used to treat asthma. The drug sample was exposed to forced degradation and found susceptible to hydrolysis and oxidative stress. The obtained Forced Degradation Products (FDP's) were resolved using an earlier developed and validated Ultra-High-Pressure Liquid Chromatography Photo-Diode-Array (UHPLC-PDA) protocol. ZLT, along with acid-and alkali-stressed samples, were subjected to Liquid-chromatography Mass-spectrometry Quadrupole Time-of-flight (LC/MS-QTOF) studies. Major degradation products were isolated using Preparative TLC and characterized using Q-TOF and/or Proton nuclear magnetic resonance (1HNMR) studies. The information obtained was assembled for structural conformation. Toxicity Prediction using Komputer Assisted Technology (TOPKAT) toxicity analyses indicated some FDP's as non-toxic when compared to ZLT. Hence, these non-toxic impurities may have bio-affinity and can be explored to interact with other therapeutic targets, to assist in drug discovery. The drug molecule and the characterized FDP's were subjected to 3-Dimensional Extra Precision (3D-XP)-molecular docking to explore changes in bio-affinity for the 5-LOX enzyme (PDB Id: 3V99). One FDP was found to have a higher binding affinity than the drug itself, indicating it may be a suitable antiasthmatic. The possibility of being active at other sites cannot be neglected and this is evaluated to a reasonable extent by Prediction of Activity Spectra for Substances (PASS). Besides being antiasthmatic, some FDP's were predicted antineoplastic, antiallergic and inhibitors of Complement Factor-D.