The role of repurposed or modified antiviral drugs has become more significant during the current global pandemic of SARS Covid-19. In the present study, four structurally analogous impurity molecules of antiviral drug Favipiravir are selected for preliminary computational investigation for assessing the structure-activity relationship. The optimized geometry and the electronic structures of the compounds are computed using Density Functional Theory as a precursor to evaluating their physical, chemical and spectral properties. The frontier orbitals analysis is performed to obtain global reactivity parameters namely, the chemical potential, absolute electronegativity, global softness, global hardness, electrophilicity, etc. The natural Bond Orbital (NBO) analysis and Mulliken analysis provided an understanding of the charge-transfer interactions of molecules. The possibilities of intermolecular interactions of the drug systems with the receptors are also visualized using the electrostatic potential maps (MEP) derived from the DFT computations. The physiochemical properties are assessed computationally using SwissADME webtool to correlate the structural aspects of the compounds with their biological responses. Useful parameters namely flexibility, lipophilicity, size, polarity, solubility and saturation were also computed to evaluate the therapeutic activity or drug-likeness.

DND-1 is a process-related impurity associated with the antiarrhythmic drug Dronedarone (DND). The quantification of drug impurities is an important part of the drug development process and there is no estimation technique reported so far for DND-1. In this work, two facile and responsive spectrophotometric methods have been developed for the assaying of DND-1. The proposed methods are then validated as per ICH guidelines for precision and accuracy. The methods were simple, fast, and free from extraction steps. The methods also enjoy trace level limits of detection and quantification and could be used for the routine quality control analysis of DND-1.

1-methyl-5,5-diphenylimidazolidine-2,4-dione (methyl phenytoin) is an intermediate impurity created en-route the commercial manufacture of epileptic drug phenytoin.Ab-initio computational modeling and spectrophotometric techniques are employed to examine molecular geometry and electronic structure to envisage possible structure-activity relationship in 1-methyl-5,5-diphenylimidazolidine-2,4-dione. Comparative studies show satisfactory consilience between theoretical and experimental approaches. According to DFT studies, the molecules are visualized to dimerize via hydrogen bonding. The two phenyl rings are not coplanar as evidenced by the dihedral angles between benzene rings and imidazole ring. The extent of intermolecular hydrogen bonding has been reduced due to methyl substitution at N1 and this assumes importance as anticonvulsant property is directly proportional to the extent of hydrogen bonding. A relatively high HOMO-LUMO energy gap of 5.9 eV implies good thermodynamical stability and a prospect of impurity being carried over during commercial drug manufacturing.Further, the presence of methyl substitution closer to the bio-toxic face opens up a prospect of title molecule being studied as an alternate drug with marked anti-epileptic action and less or no toxicity.

Objective: Two simple and sensitive techniques - one spectrophotometric and one titrimetric- have been developed for the determination of 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo[d]azepin-2-one) commonly known as ivabradine impurity-9 (IVA-9). Methods: The spectrophotometric method is based on the oxidation of drug impurity by excess cerium (IV) sulphate in acidic medium and the subsequent reaction of the remaining Ce(IV) with a known amount of ferrous ammonium sulphate. The resultant ferric ion is then made to react with thiocyanate in acid medium to form a brown coloured complex which is analyzed spectrophotometrically against the reagent blank. In the volumetric method, the un-reacted Ce(IV) is titrated against standard ferrous ammonium sulphate to estimate the quantity of IVA-9. Results: The colored complex showed an absorption maximum at 479 nm when measured spectrophotometrically. The stated methods are validated statistically using the International Council for Harmonization guidelines-ICH Q2(R1) for precision and accuracy. The method showed a linear response from 0.5 to 100µg/ml with a correlation coefficient of 0.9985 Conclusion : No estimation techniques have been reported to date for the determination of this molecule. The proposed techniques may be used for the routine quantification in its pure form and also in presence of its parent drug molecule Ivabradine.

Detection and qualification of unknown impurities during commercial drug synthesis have been mandated by the regulatory authorities. 3,3'-(propane-1,3-diyl)bis(7,8-dimethoxy-1,3,4,5-tetrahydro-2H-benzo [d]azepin-2-one) in short IVA-9, is one such process-related impurity formed during the synthesis of cardiotonic drug Ivabradine. The structure and properties of this molecule have not been explored yet. A suggestive reaction route for the chance formation of IVA-9 during the commercial synthesis of parent drug molecule has been reported in this article. Further, the optimized geometry and vibrational studies have been computed using Gaussian 09. Experimental FTIR scan has also been performed and values show satisfactory consilience with the computational data. The frontier orbital energies and energy band gaps of the reaction fragments and products were computed. The evaluation of ADME parameters such as absorption, distribution, metabolism, and excretion are performed using SwissADME tool to assess the drug-likeness and medicinal chemistry friendliness. Six physiochemical parameters namely flexibility, lipophilicity, size, polarity, solubility and saturation and their critical limits are depicted using the bioavailability radar of the programme to provide insights into pharmacokinetic properties such as human gastrointestinal absorption (HIA), blood-brain-barrier (BBB) permeability, total polar surface area (TPSA) and inhibitor action to important cytochromes etc.

Ab-initio computational study of antihemorrhage drug molecule diethylammonium 2,5-dihydroxybenzene sulfonate, popularly known as ethamsylate, has been attempted using Gaussian 09. The optimized molecular geometry has been envisaged using density functional theory method at B3LYP/6-311 basis set. Different geometrical parameters like bond lengths and bond angles were computed and compared against the experimental results available in literature. Fourier transform infrared scanning of the title molecule was performed and vibrational frequencies were also computed using Gaussian software. The presence of O-H-O hydrogen bonds between C6H5O5S-anions and N-H-O hydrogen bonds between anion and cation is evident in the computational studies also. In general, satisfactory agreement of concordance has been observed between computational and experimental results.

Objective: Spectrophotometric investigation of 4-nitro-2-phenoxyaniline (4N2PA), a probable intermediate during the synthesis of anti-inflammatory drug nimesulide, both in pure form and in the presence of nimesulide has been attempted. Methods: 4N2PA on diazotization followed by coupling with 8-hydroxyquinoline produces a crimson-colored complex which changes to deep violet on diluting with ethanol. Results: The complex showed maximum absorbance at 560 nm when evaluated spectrophotometrically with a detection limit of 0.005 μg/ml and quantification range of 0.05-3.0 μg/ml. The method has been statistically evaluated with respect to the International Council for Harmonisation guidelines and found to be accurate and precise. Conclusion: Pure tablet formulations of nimesulide do not respond to the method; however, the presence of minute amounts of 4N2PA in the drug as added impurity could be spectrophotometrically analyzed. Hence, the authors suggest that the reported technique could be a marker test for detecting the presence of 4N2PA in nimesulide formulations.

Asian Journal of Chemistry, a Multidisciplinary Chemistry Journal is an Peer Reviewed International Journal and publishes from India. The journal has been established since January 1989 on a firm foundation of International Quality Research. This Journal encompasses all branches of chemistry and its sub – disciplines like Pharmaceutical, Biological activities of Synthetic Drugs, Environmental Chemistry, Biochemistry, Polymer Chemistry, Petroleum Chemistry, and Agricultural Chemistry, etc.

A rapid, simple, accurate, and sensitive visible spectrophotometric method for the determination of trace amounts of hydrogen peroxide in acidic buffer medium is reported. The proposed method is based on the oxidative coupling of Ampyrone with dibenzazepin hydrochloride by hydrogen peroxide in the buffer medium of pH 4.0 which is catalyzed by ferrous iron. The blue-colored product formed with maximum absorption at 620 nm was found to be stable for 2 h. Beer’s law is obeyed for hydrogen peroxide concentration in the range of 0.03–0.42 μg ml−1. The optimum reaction conditions and other important optical parameters are reported. The molar absorptive and Sandell’s sensitivity are found to be 5.89 × 104 mol−1 cm−1 and 0.57 g/cm2, respectively. The interference due to diverse ions and complexing agents was studied. The method is successfully applied to the determination of hydrogen peroxide in green plants satisfactorily.

A new facile and sensitive spectrophotometric determination of Pindolol (PDL), a beta blocker drug has been developed and validated. The method was based on the reaction between pindolol and K-3 [Fe (CN)(6)] in presence of FeCl3 to form Prussian blue. The absorbance values were recorded at 700 nm and a calibrated graph was constructed. A dynamic Beer's law range was observed in the range 0.125-2.5 mu g mL(-1) with a detection limit of 0.03 mu g mL(-1) and a quantitation limit of 0.08 mu g mL(-1). Various experimental parameters such as effect of solvents, stability, interference effects due to excipients etc were studied. The reproducibility of this methods were checked by six replicate determinations at 1.0 mu g ml(-1) PDL and the standard deviation was found to be between 0.20 and 0.42 %. The results were statistically compared with those of the reference/literature method by applying Student's t-test and F-test. The sensitivity, simplicity, temperature independence and stability of the colored product are the advantages of the proposed method and it is also free from extraction steps and use of carcinogenic solvents.