Dr. Anil Kumar S.

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.

Objective: Two simple and sensitive techniques-one spectrophotometric and one titrimetric-have been developed for the determination of 3,3'-(propane-l,3-diyl)bis(7,8-dimethoxy-l,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(Rl) 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 the presence of its parent drug molecule Ivabradine. © 2019 The Authors.

A facile and highly responsive spectrophotometric method for the quantification of ultra-trace quantities of chromium(VI) is described. The proposed method is derived from the oxidation of iminodibenzyl (IDB) with chromium in strong acid medium to get a blue coloured product, having λmax at 690 nm. Stability of the colour developed is found to be around 48 h at room temperature. Beer’s law range is observed between 0.02-0.35 µg mL-1 of chromium concentration. The coefficients of molar absorptivity and Sandell’s sensitivity are found to be 1.03 × 105 L mol-1 cm-1 and 0.000523 µg cm-2, respectively where as the detection limit is 0.9 ng mL-1. The method has been optimized for reaction conditions and optical parameters. Tolerance limits for various interfering ions were studied. The efficiency of the method was shown by successful determination of traces of chromium in alloy steel samples. © 2017, Chemical Publishing Co. All rights reserved.

<p>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. © Springer Science+Business Media B.V. 2012.</p>