Green and Smart Quantitative Quality Control for Veterinary Mixture of Ivermectin and Clorsulon; Ecological Evaluation of Spectral Analyses via Analytical Eco-Scale, Green Analytical Procedure Index and Analytical GREEnness Metric Approaches.

Abstract

Global financial market is still highly threatened by bovine fasciolosis; a parasitic infection, that targets cattle, mainly in tropical regions. Binary combination of Ivermectin (IVER) and Clorsulon (CLO), in challenging concentration ratios, is typically indicated for treatment and control of fasciolosis. Present study aims at smart simultaneous spectrophotometric assay of both compounds at their high ratio in marketed formulation and synthetic mixtures, without any prior separation. Furthermore, their greenness profile was evaluated and compared with previous reported assay methods including the official one. Mathematical-based proposed methods are Dual wavelength, Induced Dual wavelength and First Derivative Ratio methods. Each is developed, optimized and applied to determine simultaneously IVER and CLO at linear ranges of 1-30 and 5-40 μg/mL, respectively. They have been validated according to ICH guidelines. Statistical student t- and F-tests, compared the proposed methods with USP chromatographic technique. Ecological appraisal is accomplished using three independent metrics; Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical GREEnness Metric Approach (AGREE). Satisfactory recoveries, ICH compliance and adherence of proposed methods to the ecological safety margin are achieved. Developed methods are eco-friendly, cost effective and can accomplish a routine quantitative quality control for concurrent determination of both drugs. Veterinary antimicrobials need analytical quality control using safer and green methodologies. Data manipulated spectral analyses of IVER and CLO, in ratio 1:10%v/v, is developed and optimized. AES, GAPI and AGREE approaches illustrate the high green compliance in respect to literary reported assays. Furthermore, the United States Pharmacopeia (USP) assay for IVER and CLO in injectable dosage form depends on analysis of each drug separately in the presence of the other drug but it cannot determine both drugs simultaneously at the same time.