An Eco-Friendly HPLC-DAD Determination of Corticosteroids Combined with Other Therapeutic Compounds in Bulk and Topical Formulations: Greenness and Whiteness Assessment

Creams are among the most analytically challenging dosage forms both in product analysis and in cleaning validation. This is especially true when highly lipophilic drugs are the active ingredients. The case is getting more challenging with the greenness emerges as an evaluation criterion where solvents and wastes should be minimized. Green methods are difficult to achieve with lipophilic drugs and creams that may encounter high carry-over tendency. In this study, an ecofriendly RP-HPLC-DAD method was developed for the determination of hydrocortisone acetate (HCA), mometasone furoate (MOM), betamethasone valerate (BTM), clotrimazole (CLT) and oxytetracycline (OXT) in the presence of miconazole as examples of lipophilic drugs commonly formulated in creams. The separation was performed on a C₁₈ (5 µm, 150 × 4.6 mm ID) column using methanol–water (80 : 20, v/v) as a mobile phase and a photo-diode array detector. The method was validated according to ICH guidelines. Greenness and whiteness were assessed by NEMI, GAPI, AGREE, Eco-scale, and the RGB 12 model and compared to currently available methods. The developed method was found linear with r² > 0.99 within the range of 0.05–9.00 HCA, 0.1–9.0 MOM, 0.2–9.0 BTM, 0.6–9.0 CLT, and 5.0–9.0 µg/mL OXT. The accuracy (98.4 ± 1.7)–(102.3 ± 1.5) and precision (CV < 10%) were in acceptable ranges while retaining high sensitivity (LOD down to 15 ng). The proposed method proved to be environmentally friendly by applying different greenness and whiteness algorithms and was successfully applied to different cream formulations. In conclusion, the developed method outperforms currently available methods for the determination of tested lipophilic compounds in creams.