Novel gas-diffusion microextraction followed by gas chromatography coupled to tandem mass spectrometry methodology for the determination of fragrance allergens in cosmetic products

An efficient sample preparation method using gas-diffusion microextraction (GDME) followed by gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) is proposed for the first time to determine fragrance allergens in both aqueous and alcohol-based cosmetic products. The most significant GDME parameters were optimized, starting with extraction temperature as a preliminary experiment. Subsequently, an experimental design was performed to evaluate the influence of six parameters: acceptor solution volume, acetonitrile percentage in the acceptor solution, sample dilution, salting-out effect, extraction time, and sample volume. Under the optimized conditions, the method was validated in terms of linearity, precision, trueness, obtaining a good performance. The validated methodology was applied to twelve real cosmetic samples, demonstrating the widespread occurrence of these allergens in cosmetics. Notably, lilial, a compound prohibited by Regulation EC No 1223/2009, was detected in one cosmetic product (460 μg mL^-1); and the concentrations of some of the target fragrance allergens in some samples reach values above 1000 μg mL^-1. This methodology represents a sustainable and practical approach, supported by AGREEPrep and BAGI metrics, respectively.