Application of Quality by Design in RP-HPLC for Robust Impurity Profiling and Stability Assessment of Doxylamine

The primary purpose of this research was to create and validate a doxylamine detection method using reverse phase high performance liquid chromatography (RP-HPLC) for use in pharmaceutical formulations and bulk materials. Quality by design (QbD) served as the inspiration for this approach. The method was developed by running a C18 column at 1-mL/min through a mobile phase of 60 parts methanol to 40 parts 0.1% OPA water (pH 2.8). The detection was done with a UV detector set to 259 nm. All requirements for system applicability were satisfied by the suggested approach, including an acceptable asymmetry factor and an adequate number of theoretical plates. A correlation coefficient (R2) of 0.9990 was used to confirm linearity over a concentration of 10–50 g/mL. The approach showed good accuracy by a mean %recovery ranging from 99.59–101.45% and a %RSD between 0.11 and 0.81. Precision tests conducted both intraday and across days showed that the medication content stayed within allowable bounds. The approach was found to be robust, with only minor variations in flow rate, mobile phase composition, and detecting wavelength significantly affecting the accuracy and specificity. A 0.71 g/mL LoQ and a 0.23 g/mL LoD were determined to be analytical limits of detection and quantification, respectively. This study substantiates the development of a reliable, long-lasting, and cost-effective QbD-based RP-HPLC method suitable for the comprehensive analysis of doxylamine in tablet formulations and bulk dosage