DEVELOPMENT AND VALIDATION OF UV SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF DOLUTEGRAVIR BY USING QUALITY BY DESIGN (QbD) APPROACH

Abstract

Spectrophotometric methods were developed according to Quality by Design (QbD) approach as per ICH Q8(R2) guidelines for estimation of dolutegravir. QbD approach was carried out by varying various parameters, and these variable parameters were designed into Ishikawa diagram. The present work deals with the development of sensitive, simple, accurate, precise and cost-effective UV-spectrophotometric method for the determination of dolutegravir, an anti-retroviral drug, in bulk and pharmaceutical dosage form by UV spectrophotometric method as per International Conference on Harmonisation (ICH) guidelines. The critical parameters were determined by using principal component analysis as well as by observation. Estimated critical parameters in the spectrophotometric method were solvent methanol, wavelength: 260nm, slit width: 0.5, scan speed fast, sampling interval: 0.2nm and proposed method was validated for various parameters like system suitability, linearity, precision, accuracy, detection limits and quantification limits as per the International Conference on Harmonization guidelines ICH Q2(R1). The method's linearity was found to be excellent over the concentration range 5 to 25μg/ml with high correlation coefficient value of 0.999. Limits of detection and quantification were found to be 0.20μg/ml and 0.60μg/ml, respectively. The mean recovery was found to be 100.35% with low percentage relative standard deviation (% RSD) value. The precision study also has shown low % RSD value (less than 1). No interfering peaks were observed during specificity studies. A simple, rapid, sensitive, accurate, precise and inexpensive spectrophotometric method was developed for estimation of dolutegravirin bulk by using analytical quality by design (AQbD) approach. The same method is also applied for plasma samples study in bioanalytical work.