Novel Microwell-Based Spectrophotometric Assay for the Determination of Rosuvastatin Calcium in its Pharmaceutical Formulations

Tanveer      A. Wani; Ibrahim      A. Darwish; Nasr      Y. Khalil

Abstract

A novel 96-microwell-based spectrophotometric assay has been developed and validated for the determination of rosuvastatin calcium (ROS-Ca) in tablets. The formation of a colored charge-transfer (CT) complex between rosuvastatin calcium (ROS-Ca) as n-electron donor and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor was investigated, for the first time. The spectral characteristics of the CT complex have been described, and the reaction mechanism has been proved by computational molecular modeling. The reaction was employed in the development of a novel microwell-based spectrophotometric assay for the determination of ROS-Ca in its pharmaceutical formulations. The proposed assay was carried out in 96-microwell plates. The absorbance of the colored-CT complex was measured at 460 nm by microwell-plate absorbance reader. The optimum conditions of the reaction and the analytical procedures of the assay were established. Under the optimum conditions, linear relationship with good correlation coefficient (0.9987) was found between the absorbance and the concentration of ROS-Ca in the range of 10-100 μg/well. The limits of detection and quantitation were 2.6 and 7.85 μg/well, respectively. No interference was observed from the additives that are present in the pharmaceutical formulation or from the drugs that are co-formulated with ROS-Ca in its combined formulations. The assay was successfully applied to the analysis of ROS-Ca in its pharmaceutical dosage forms with good accuracy and precision. The assay described herein has great practical value in the routine analysis of ROS-Ca in quality control laboratories, as it has high throughput property, consumes minimum volume of organic solvent thus it offers the reduction in the exposure of the analysts to the toxic effects of organic solvents, and reduction in the analysis cost by 50- fold. Although the proposed assay was validated for ROS-Ca, however, the same methodology could be used for any electron- donating analyte for which a CT reaction can be performed.

Keywords: Rosuvastatin calcium, Charge-transfer reaction, Spectrophotometry, Microwell-based assay, High throughput analysis, ROS-Ca, computational molecular modeling, DDQ, π-electron acceptor, electron-donating analyte