**1. Introduction**

The cosmetic industry is one of the fastest growing markets in the world, due to a high demand for cosmetics and personal care products. Manufacturers must innovate to o ffer attractive and safe products for consumers to stay ahead in a highly competitive sector. Cosmetic formulations usually include a large number or organic compounds, such as fragrances, preservatives, antioxidants, plasticizers, or surfactants among others. One type of these compounds are the ultraviolet filters (UV filters). These substances are intended to protect consumers against the harmful solar radiation and, although their presence is especially important in sunscreens, they can be found in a broad range of daily care products such as creams, hair-care products, lip protectors, make-up, and many others. The widespread inclusion of UV filters in personal care and consumer products increases the human exposure to these compounds. Some of them are considered as endocrine disruptors, with high bioaccumulative properties. In fact, some of them have been recently detected in human breast milk. Nowadays, according to the Annex VI of the Regulation EC No 1223/2009 [1], 26 organic UV filters are allowed for their use in the formulation of cosmetic products, being the maximum concentration permitted in the final product up to 10% (w/w). It is important to note that the Regulation regarding cosmetic products is being continually updated, with the restriction and even prohibition of several compounds each year. Therefore, the cosmetic sector demands the development of reliable, fast and easy to implement analytical methodology to analyze a broad range of cosmetics ingredients. One major drawback for the analysis of cosmetics is sample preparation, since the cosmetic matrices are complex and varied. Besides, the concentration of the different ingredients in cosmetic formulations usually ranges several orders of magnitude, from the ng g<sup>−</sup><sup>1</sup> to thousands of μg g<sup>−</sup>1.

Most of the reported methodologies for the determination of UV filters in cosmetics deal with the simultaneous analysis of few target compounds. Regarding the sample preparation, solid-liquid or liquid–liquid extraction, or simple dilution, have been the most employed procedures [2–4]. However, since cosmetics are complex mixtures of ingredients, the direct dilution of the samples can negatively affect the chromatographic determination and the chromatographic system, producing damage in the injector, column and detector. Therefore, the use of sample preparation techniques which imply an in-situ clean-up step is a good approach. In this way, matrix solid-phase dispersion (MSPD) has been proposed for the extraction of different families of cosmetic ingredients such as fragrances, preservatives or dyes [5–7].

New trends in sample preparation are focused on the development of miniaturized procedures which complies with the green chemistry principles [8,9], and techniques such as ultrasound-assisted emulsification microextraction (USAEME) or single drop microextraction have been developed [10,11] for the determination of parabens of phthalates. In this way, a miniaturization of the classical MSPD, micro-MSPD (μ-MSPD), employing low-cost material, low amount of sample and organic solvent consumption, has been successfully proposed for the extraction of different compounds such as synthetic musks, preservatives, fragrance allergens, or dyes [12–15] in cosmetics and personal care products. However, to the best of our knowledge MSPD and μ-MSPD have never been applied for the determination of UV filters.

Regarding the analytical determination of UV filters in cosmetic samples, LC-DAD has been the most employed technique [2]. However, the use of other detectors, such as MS, and especially the use of triple quadrupole working under MS/MS provides improved selectivity and sensitivity [16,17].

The main goal of this work is the development of an analytical methodology based on μ-MSPD-GC–MS/MS for the simultaneous determination of 14 multiclass UV filters in cosmetic samples. The main experimental parameters affecting extraction, such as the type of sorbent, and amount and type of extraction solvent have been optimized by means of experimental design. The method was validated and applied to a broad range of cosmetic and personal care products to quantify not only UV filters, but also other families of compounds such as fragrances, preservatives, plasticizers, and synthetic musks, allowing the simultaneous analysis of 78 compounds with very different chemical nature in a single extraction and chromatographic run.

### **2. Materials and Methods**

#### *2.1. Chemicals, Reagents and Materials*

The studied UV filters, their Chemical Abstracts Service (CAS) number, retention times, and MS/MS transitions are summarized in Table 1. Target fragrance allergens, preservatives, plasticizers and synthetic musks are shown in Table S1. Ethyl acetate, acetonitrile (ACN) and isooctane were provided by Sigma-Aldrich Chemie GmbH (Steinheim, Germany), methanol (MeOH) was supplied by Scharlab (Barcelona, Spain), and acetone was provided by Fluka Analytical (Steinheim, Germany). Florisil (60–100 μm mesh), and glass wool were purchased from Supelco Analytical (Bellefonte, PA, USA), and sand (200–300 μm mesh) and anhydrous sodium sulphate, Na2SO4, (99%) from Panreac (Barcelona, Spain). Individual stock solutions of all the compounds were prepared in acetone, isooctane or methanol. Further dilutions and mixtures were prepared in acetone (spike solutions) or acetonitrile

(calibration study). Solutions were stored in amber glass vials at −20 ◦C. All solvents and reagents were of analytical grade.


**Table 1.** Studied ultraviolet (UV) filters. CAS number, retention time and mass spectrometry (MS)/MS transitions.

> a CE: collision energy; underlined SRM transitions: quantification transitions.

Metallic, glass materials, dispersing agents (Florisil and sand), Na2SO4 and glass wool were maintained at 230 ◦C for 12 h before use to eliminate possible phthalate contamination. All materials were allowed to cool down, wrapped with aluminum foil, and Florisil, sand, and Na2SO4 were kept in desiccator.
