Analytical quality by design driven RP HPLC method development and validation for quantification of paracetamol in pharmaceutical tablets

Abstract

Development and validation of an Analytical Quality by Design (AQbD) based RP-HPLC method for estimating Paracetamol content in tablets using Central Composite Design (CCD). Chromatographic resolution was attained with the help of an Agilent TC-C18 column (250 mm × 4.6 mm, 5 μm), where a mobile phase consisting of Water: Acetonitrile: Methanol (80:15:5, v/v/v) was adjusted with a pH value of 6.5, and triethylamine was added to adjust pH with a Flow rate 1.0 mL/min, and detection was done at 254 nm. Parameters such as organic modifier concentration, pH, and flow rate were optimized using Central Composite Design (CCD). The developed method was validated as per ICH Q2(R2) guidelines. The optimized HPLC method provided a well-defined and symmetric peak of Paracetamol with acceptable method performance characteristics. The optimized linearity range extended from 18 to 42 µg/mL with a very high correlation coefficient (r²) of 0.9995. The optimized %RSD values were 0.66% for repeatability and 1.75% for intermediate precision. In terms of accuracy, the mean % Recovery value was 101.58%, while the %RSD was 0.70%. An Excipient interference was not noted, and robustness testing also revealed good performance within the design space. Flow rate and organic modifier concentration affected the method performance significantly. The AQbD-based RP-HPLC technique used for quantification of Paracetamol in tablets was found to be simple, accurate, precise, robust, and reliable. The use of AQbD and CCD helped in optimizing the method systematically.