Integrating DFT-assisted optimization into HPLC-DAD method development: simultaneous determination of four...

An HPLC-DAD method was established for the simultaneous determination of four synthetic compounds-diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO), Ethyl phenyl(2,4,6-trimethylbenzoyl)phosphinate (TPO-L), (Di-p-tolylphosphoryl)(mesityl)methanone (TMO), and Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (XBPO)-in nail gel polish, addressing potential safety risks such as sensitization and reproductive toxicity. DFT calculations were utilized as theoretical support to screen extraction solvents by evaluating the thermochemical stability, photochemical stability, and homolysis propensity of target molecules, as well as to determine quantification wavelength under complex mobile phase conditions. For sample purification, a unified QuEChERS procedure utilizing PSA (primary-secondary amine) was optimized, with the aim of removing nail gel polish components that interfere with detection or irreversibly reduce column efficiency. Method validation confirmed satisfactory linearity (R² ≥ 0.9999) across specified concentration ranges. Analysis of import and export products revealed detectable levels of at least one of TPO, TPO-L, TMO, and XBPO in 67 samples, which suggests a possible trend: as regulatory bans in the European Union (EU) and other regions came into force, the use of TPO declined, giving way to increased use of the alternatives, TMO and TPO-L, followed by the gradual employment of XBPO in nail gel polish products. Nevertheless, potential risks arising from photoinitiators structurally similar to TPO persist, highlighting the relevance of this reliable analytical approach for cosmetic safety surveillance.