Green and lean: A validated RP-HPLC-VWD method for simultaneous determination of hydroquinone, methylparaben, fluocinolone acetonide, and propylparaben.

Abstract

This study investigated the optimization, development, and validation of an accurate, precise, and sensitive reversed-phase high-performance liquid chromatographic technique with variable-wavelength detection (RP-HPLC-VWD) method for the rapid determination of four active ingredients (APIs) of hydroquinone (HYQ), methylparaben (MP), fluocinolone acetonide (FLN), and propylparaben (PP) in pharmaceutical dosage forms. The optimized chromatographic conditions consisted of a mobile phase of a mixture of acetonitrile and a sodium heptane-1-sulfonate buffer (pH 3.5) with a BDS C18 column (5 μm, 250 mm × 4.6 mm) and wavelength detection at 254 nm. The method revealed excellent linearity (R2 > 0.999 for all analytes), accuracy (recovery ranging from 99.0 to 101.5% across three concentration levels), high precision, with a repeatability RSD% of <0.3% for all APIs, and robustness/ruggedness confirmed within the ICH-recommended limit of <2.0% (RSD% range from 0.218% to 1.367%). To enhance process efficiency, Lean Six Sigma methodology was implemented, incorporating the process capability index (Cpk), which yielded values greater than 1.0, indicating a capable and stable process. The RP-HPLC-VWD method for HYQ/MP/FLN/PP achieves an excellent balance between superior analytical performance and practicality, while also revealing a good environmentally sound approach. The accompanying tools complement each other perfectly, with high performance of RAPI (95.0%)/ BAGI (77.5%) highlighting the strengths and acceptable satisfaction level of EPPI (EI = 76.7% and PPI = 55.0%) and Multi-color Assessment platform (MA = 61.1%) and Red-Green-Blue (72.5%) as a whiteness evaluation tool.