Fractional factorial and central composite design for implementation of risk and DoE-based enhanced AQbD approach to eco-friendly HPTLC method for estimation of dalfampridine in pharmaceutical dosage forms and human plasma

• Published in: Journal of the Iranian Chemical Society 2022-06, Vol.19 (6), p.2263-2277
• Main Authors: Prajapati, Pintu B., Patel, Urmi R., Shah, Shailesh A.
• Format: Article
• Language: English
• Subjects: Analytical Chemistry; Biochemistry; Blood plasma; Chemistry; Chemistry and Materials Science; Correlation coefficients; Dosage; Human motion; Inorganic Chemistry; Mathematical analysis; Multiple sclerosis; Optimization; Organic Chemistry; Original Paper; Parameter identification; Pharmaceutical industry; Pharmaceuticals; Physical Chemistry; Plasma; Quality control; Recovery; Response surface methodology; Risk assessment; Silica gel
• ISSN: 1735-207X; 1735-2428
• DOI: 10.1007/s13738-021-02445-z

Dalfampridine is a potassium channel blocker used for the improvement of motor function in patients with multiple sclerosis. Numerous analytical techniques have been published in the literature for estimation of dalfampridine but no report has been found in the literature for estimation of dalfampridine in pharmaceutical dosage forms and human plasma by the HPTLC method. Hence, an eco-friendly HPTLC method has been developed for the estimation of dalfampridine using risk and the DoE-based enhanced AQbD approach. The risk-based AQbD approach was applied by identification of method risk parameters followed by their risk assessment in method development by DoE-based FFD. The DoE-based AQbD approach was implemented for optimisation of high-risk method parameters by response surface methodology using CCD. The MODR and control strategy was framed for mitigation of risk of high-risk method parameters and low-risk life cycle management of developed method. The chromatogram was developed using silica gel G F254 as stationary phase and methanol–water-diethylamine (9.5:0.5:0.2, V/V) as mobile phase keeping saturation time of 10 min. The developed method was validated as per ICH Q2 (R1) guideline. The linearity range of the dalfampridine was found to be 200–1000 ng/band with a correlation coefficient of 0.995 both in bulk drug and human plasma. The % recovery of spiked standard from the pre-analysed sample was found to be in the range of 98–102%. The % recovery was found to be more than 80% from human plasma. The %RSD for all precision studies was found to be less than 2.0. The developed method was applied for the assay of pharmaceutical dosage forms, and results were found in compliance with the labelled claim. The developed method can be used as an eco-friendly alternative for routine bio-analysis and quality control of pharmaceutical dosage forms of dalfampridine in the pharmaceutical industry.