Castiñeira Landeira, AnaGómez-Feas, ÁngelCarro Díaz, Antonia MaríaDagnac, ThierryAlmeida, Paulo J.Llompart Vizoso, María del Pilar2025-05-212025-05-212025Castiñeira-Landeira, A., Gomez-Feas, A., Carro, A. M., Dagnac, T., Almeida, P. J., Llompart, M. (2025). Novel gas-diffusion microextraction followed by gas chromatography coupled to tandem mass spectrometry methodology for the determination of fragrance allergens in cosmetic products. "Advances In Sample Preparation", vol. 14, 00187https://hdl.handle.net/10347/41684An 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.eng© 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by- nc/4.0/). Attribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/GDMEGC–MS/MSFragrance allergensCosmetic productsSample preparationAnalytical metricsAGREEPrep2301 química analíticajournal article10.1016/j.sampre.2025.1001872772-5820open access