Screening natural deep eutectic solvent-based extraction to analyze illegal skin-whitening ingredients in cosmetics using HPLC and LC-MS/MS.

Despite regulatory bans on hazardous substances such as hydroquinone, glucocorticoids, and retinoids, these compounds are still detected in cosmetic products, underscoring the need for reliable analytical methods. This study evaluated four sample preparation approaches for detecting banned ingredients: ultrasound-assisted extraction (UAE), "Quick, Easy, Cheap, Effective, Rugged, Safe" (QuEChERS), solid-phase extraction (SPE), and natural deep eutectic solvents (NaDESs). High-performance liquid chromatography with diode array detection (HPLC-DAD) revealed low recoveries for QuEChERS and SPE. In contrast, NaDESs prepared with choline chloride (ChCl) or betaine as hydrogen bond acceptors (HBAs) and 1,3-propanediol as a hydrogen bond donor (HBD) achieved significantly higher recoveries. In particular the ChCl-1,3-propanediol NaDES (1:4 M ratio) provided recoveries of 83.96-105.45%. UAE using methanol yielded comparable recoveries (91.29-106.81%), but the NaDES approach was more environmentally sustainable due to reduced organic solvent use. Method validation following International Conference on Harmonization (ICH) guidelines confirmed acceptable sensitivity (limit of detection: 0.27-1.59 μg/mL; limit of quantification: 0.81-4.81 μg/mL), recovery, linearity, precision, and accuracy. Target analytes were further verified using liquid chromatography-tandem mass spectrometry. These results demonstrate the feasibility of applying green solvents in cosmetic analysis and highlight a sustainable, effective method for detecting banned skin-whitening agents.