Eco-friendly and green chromatographic method for the simultaneous determination of chlorocresol and betamethasone dipropionate in topical formulations using Box–Behnken design

Betamethasone dipropionate topical formulations are using to treat anti-inflammatory skin diseases such as dermatitis, eczema, and psoriasis. The current research study confers the eco-friendly toward green chemistry and stability-indicating RP-UHPLC method for the simultaneous determination of chlorocresol (CCL) and betamethasone dipropionate (BTD) in topical formulations (cream and ointment). The CCL and BTD were accurately quantitated by employing beclomethasone dipropionate (BCD) as an internal standard. The developed method was optimized utilizing QbD-based Box–Behnken Design (BBD) prior to method validation for the intended purpose. The critical quality attributes (CQAs) and critical method parameters (CMPs) identified and executed 15 design of experiments (DoEs). The foremost influencing factors were fine-tuned and optimized using graphical and numerical evaluation. The chromatographic separation was accomplished on Acquity UPLC BEH C 18 , 100 mm × 2.1 mm, 1.7 µm column with potassium phosphate buffer (0.02 M) and acetonitrile (ACN) using gradient elution with a runtime of 8 min. The set flow rate and injection volumes were 0.4 mL/min and 5 µL, respectively. The detection was made at 240 nm and maintained column oven temperature at 40 °C. The analytical method was validated as per the current ICH guideline Validation of Analytical Procedures: Text and Methodology Q2(R1). The linearity ranges for CCL, BTD, and BCD were 20.4–61.1, 10.3–30.8, and 10.4–31.1 µg/mL with correlation coefficients of > 0.999. As revealed, the method was superior accuracy with % recovery for CCL 98.6–101.5 and BTD 99.6–101.6 at three different levels. The results dictate the fitness of the method for the routine quality control determination of CCL and BTD from its commercial topical formulations. The proposed method with a low flow rate and less runtime benefits to analyze high throughput quality control samples with less solvent consumption, and it helps the environment by supporting the green chemistry concept.