Desarrollo de métodos analíticos para el control de filtros UV de naturaleza orgánica en productos cosméticos para la protección solar.

RESUMEN El actual deterioro de la capa de ozono ha provocado un incremento de la radiación UV solar que llega a la Tierra, que hace necesaria una mayor protección con el fin de evitar efectos perjudiciales para la salud. El uso de productos cosméticos para la protección solar que incorporan filtros UV en su formulación podría contribuir a prevenir estos efectos dañinos. El control analítico de estos productos es necesario, ya que debe garantizarse su eficacia y seguridad. Sin embargo no existen métodos oficiales para su análisis, por lo que el desarrollo de métodos analíticos rápidos y exactos para el control del producto cosmético acabado es de gran interés, y constituye el objeto de esta Tesis Doctoral. Se ha puesto especial atención en el desarrollo de métodos en los que se utilicen reactivos inocuos o de baja toxicidad, reduciendo igualmente la cantidad de reactivos utilizada y minimizando la generación de residuos, con el fin de proponer métodos de análisis limpios, y así cumplir con la actual tendencia de la química analítica denominada Química Analítica Verde (Green Analytical Chemistry, en inglés). Se han propuesto métodos automatizados basados en el uso de la espectroscopía de absorción UV/VIS, fluorimetría y quimioluminimetría. La automatización de los procedimientos permite aumentar la rapidez del análisis. Las características analíticas de estos métodos son adecuadas para el control analítico de los filtros UV en los productos cosméticos acabados. También se han desarrollado métodos de cromatografía líquida con detección UV/VIS que permiten realizar en pocos minutos la determinación simultánea de los filtros UV más utilizados a nivel internacional. Las características analíticas de estos métodos son adecuadas para el control analítico de los productos cosméticos acabados. Además, en el último capítulo de esta Tesis Doctoral, se ha puesto a punto un método analítico para la determinación en orina de usuarios de productos cosméticos para la protección solar de uno de los filtros UV más utilizados, con el fin de estudiar los mecanismos de excreción y acumulación en el organismo y facilitar información sobre su posible efecto toxicológico. __________________________________________________________________________________________________Damage to the ozone layer has led to an increment in the solar UV radiation reaching earth, which in turn makes strong protection necessary in order to prevent harmful effects on human health. The use of sunscreen cosmetics could help to prevent or minimize these harmful effects. The analytical control of these products is necessary, since their efficacy and safety must be guaranteed. However, there are no official analytical methods to be used, and thus the development of rapid and accurate analytical methods in order to control sunscreen cosmetics is, without any doubt, of high interest, and this topic is the aim of this Doctoral Thesis. Special attention has been paid in the development of methods that use harmless reagents or with low toxicity, and moreover, by reducing the amount of employed reagents and thus minimizing the volume of waste of products generated, by proposing friendly (or green) analytical methods for both the environment and operator in order to fulfil with the current tendency of the analytical chemistry known as Green Analytical Chemistry. In this sense, different automated methods based on the use of UV/VIS absorption spectroscopy, fluorimetry and chemiluminiscence have been proposed. The automation of the procedures allows increasing the sample throughput. The analytical features of these methods are very suitable for the analytical control of the UV filters in the sunscreen cosmetic products. On the other hand, different methods based on the use of liquid chromatography with UV/VIS detection have been also proposed, which allow the simultaneous determination of the worldwide most used UV filters in few minutes. The analytical features of these methods are also very suitable for monitoring the UV filters in the cosmetic products. Finally, the last chapter of this Doctoral Thesis is focused on the development of an analytical method able to determine one of the most used UV filter in urine samples coming from users of sunscreen cosmetic products, in order to study the excretion and bioaccumulation mechanisms in the human body, and thus providing information on its possible toxicological side-effects

A paper-based polystyrene/nylon Janus platform for the microextraction of UV filters in water samples as proof-of-concept

A new mix-mode cellulose-based sorptive phase is described that combines two different polymeric domains (i.e., nylon and polystyrene), thus providing simultaneous hydrophilic and hydrophobic features as a result. By analogy with Janus materials, the new paper-based sorptive phase has been named paper-based polystyrene/nylon Janus-platform (P-Ps/Ny-JP). The main advantages of the proposed P-Ps/Ny-JP are the sustainability, simplicity in synthesis, and low cost of this extraction device. The main parameters affecting the synthesis (i.e., coating procedure and polymers proportion) have been studied, and the resulting material has been characterized via scanning electron microscopy and infrared spectroscopy. As a proof-of-concept, the simultaneous extraction of fourteen UV filters of a wide range of polarity, with log P values ranging from − 0.234 to 16.129, from water samples and their determination by liquid chromatography-tandem mass spectrometry (LC–MS/MS) has been performed. The proposed methodology enables the determination of these chemicals with limits of detection from 12 to 71 ng L−1, and the precision, expressed as a relative standard deviation, was below 15%. The extraction device was applied to the analysis of real water samples likely to contain UV filters (i.e., two private swimming pool water and one seawater) and the recovery values were in the range 73–121%

Low toxicity deep eutectic solvent-based ferrofluid for the determination of UV filters in environmental waters by stir bar dispersive liquid microextraction.

[EN] In this work, a low toxicity deep eutectic solvent-based ferrofluid is presented for the first time as magnetic fluid to be used as an efficient solvent in liquid-based microextraction techniques. This ferrofluid is made of a hydrophobic deep eutectic solvent, composed by menthol and thymol in a 1:5 molar ratio as carrier solvent, and oleic acid-coated cobalt ferrite (CoFe2O4@oleic acid) magnetic nanoparticles. This material was characterized via magnetism measurement, scanning electron microscopy, infrared spectroscopy and density measurement. The determination of UV filters in environmental water samples was selected as model analytical application to test the extraction performance of this new ferrofluid by employing stir bar dispersive liquid microextraction, prior to liquid chromatography-tandem mass spectrometry analysis. The response surface methodology was used as a multivariate optimization method for extraction step. Under the optimized conditions, good analytical features were obtained, such as low limits of detection between 7 and 83ngL-1, good repeatability (relative standard deviations, RSD (%) below 15%), enrichment factors between 46 and 101 and relative recoveries between 80 and 117%, proving the good extraction capability of this ferrofluid. Finally, the method was successfully applied to three environmental waters (beach and river waters), finding trace amounts of the target UV filters. The presented low toxicity deep eutectic solvent-based ferrofluid results to be a good alternative to conventional solvents used in liquid-phase microextraction techniques.J.L.B. thanks the Generalitat Valenciana and the European Social Fund for his postdoctoral grant, and A.D. thanks the Basque Country Government for her predoctoral contract (Bikaintek 2020 Program from the Regional Minister for Economic Development and Infrastructures (order 2021–1353, file number 021-B2/2020)). Authors also thank to the Magnetism Unit of SGIker of University of Basque Country (UPV/EHU) for kindly carrying out the magnetism measurements. This article is based upon work from the National Thematic Network on Sample Treatment (RED-2018-102522-T) of the Spanish Ministry of Science, Innovation and Universities, and the Sample Preparation Study Group and Network supported by the Division of Analytical Chemistry of the European Chemical Society

Identification of the Biotransformation Products of 2-Ethylhexyl 4-(N,N-Dimethylamino)benzoate

Nowadays, 2-ethylhexyl 4-(N,N-dimethylamino)benzoate (EDP) is one of the most widely used UV filters in sunscreen cosmetics and other cosmetic products. However, undesirable processes such as percutaneous absorption and biological activity have been attributed to this compound. The in vitro metabolism of EDP was elucidated in the present work. First of all, the phase I biotransformation was studied in rat liver microsomes and two metabolites, N,N-dimethyl-p-aminobenzoic acid (DMP) and N-monomethyl-p-aminobenzoic acid (MMP), were identified by GC-MS analysis. Secondly, the phase II metabolism was investigated by means of LC-MS. The investigated reactions were acetylation and glucuronidation working with rat liver cytosol and with both human and rat liver microsomes, respectively. Analogue studies with p-aminobenzoic acid (PABA) were carried out in order to compare the well established metabolic pathway of PABA with the unknown biotransformation of EDP. In addition, a method for the determination of EDP and its two phase I metabolites in human urine was developed. The methodology requires a solid-phase extraction prior to LC-MS analysis. The method is based on standard addition quantification and has been fully validated. The repeatability of the method, expressed as relative standard deviation, was in the range 3.4–7.4% and the limit of detection for all quantified analytes was in the low ng mL−1 range

Use of Nanomaterial-Based (Micro)Extraction Techniques for the Determination of Cosmetic-Related Compounds

The high consumer demand for cosmetic products has caused the authorities and the industry to require rigorous analytical controls to assure their safety and efficacy. Thus, the determination of prohibited compounds that could be present at trace level due to unintended causes is increasingly important. Furthermore, some cosmetic ingredients can be percutaneously absorbed, further metabolized and eventually excreted or bioaccumulated. Either the parent compound and/or their metabolites can cause adverse health effects even at trace level. Moreover, due to the increasing use of cosmetics, some of their ingredients have reached the environment, where they are accumulated causing harmful effects in the flora and fauna at trace levels. To this regard, the development of sensitive analytical methods to determine these cosmetic-related compounds either for cosmetic control, for percutaneous absorption studies or for environmental surveillance monitoring is of high interest. In this sense, (micro)extraction techniques based on nanomaterials as extraction phase have attracted attention during the last years, since they allow to reach the desired selectivity. The aim of this review is to provide a compilation of those nanomaterial-based (micro)extraction techniques for the determination of cosmetic-related compounds in cosmetic, biological and/or environmental samples spanning from the first attempt in 2010 to the present

A Rapid and Sensitive Method for the Determination of Cannabidiol in Cosmetic Products by Liquid Chromatography–Tandem Mass Spectrometry

Cannabidiol is a phytocannabinoid with proven pharmacological properties that is also used in the cosmetic industry for its sebostatic and antioxidant activities, being considered a new anti-aging ally. An analytical method is proposed for the determination of CBD in cosmetic products by liquid chromatography with tandem mass spectrometry, after leaching the CBD from the cosmetic matrix with ethanol. Low instrumental limits of detection (0.22 ng mL−1) and quantification (0.74 ng mL−1) allow the determination of CBD at trace levels without needing preconcentration, whereas the wide linearity of the method allows the determination of CBD in more concentrated samples without high dilution. The method was successfully applied to the analysis of six cosmetic products and a raw material. The proposed method is suitable for the quality control of cosmetic products containing CBD, being able to quickly and easily determine this compound, ensuring that its concentration in the finished product is the desired one

High-throughput determination of oxidative stress biomarkers in saliva by solvent-assisted dispersive solid-phase extraction for clinical analysis

A reliable analytical method for the simultaneous determination of two oxidative stress biomarkers (i.e., 8‑hydroxy-2′-deoxyguanosine (8-oxodG) and 8‑hydroxy-2′-deoxyadenosine (8-oxodA)) in saliva samples is presented. These biomarkers are produced by an oxidative DNA damage and have gained prominence in the field of medicine as early diagnostic and disease control tools. The method is based on solvent-assisted dispersive solid-phase extraction (SA-DSPE) as a clean-up step, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For this purpose, a commercial polymer with a hydrophilic-hydrophobic balance has been used as extraction phase. This balance makes the material suitable for extracting compounds from polar matrices such as saliva. Those variables involved in the extraction were optimized by a Box-Behnken design, whereas those variables affecting the desorption were optimized by a Doehlert design, except the desorption solvent that was optimized by using a Simplex-Centroid design. The method was successfully validated, showing a good linearity at least up to 20 ng mL−1, limits of detection and quantification at the low ng mL−1 level, and good precision values (< 15%). Standard addition calibration was employed to correct the observed matrix effects. Finally, this new approach was successfully applied to saliva samples from nine volunteers, three of them with type II diabetes, obtaining notable differences in the concentration values between both groups. The proposed methodology overcomes some of the drawbacks of the only previous work with the same purpose, such as the time-consuming procedure and the consumption of large volumes of organic solvents. To increase the sample throughput and reduce the analysis time, a thermostatic stirrer that allows the extraction of several samples simultaneously was used

Sunscreen Products as Emerging Pollutants to Coastal Waters

A growing awareness of the risks associated with skin exposure to ultraviolet (UV) radiation over the past decades has led to increased use of sunscreen cosmetic products leading the introduction of new chemical compounds in the marine environment. Although coastal tourism and recreation are the largest and most rapidly growing activities in the world, the evaluation of sunscreen as source of chemicals to the coastal marine system has not been addressed. Concentrations of chemical UV filters included in the formulation of sunscreens, such as benzophehone 3 (BZ-3), 4-methylbenzylidene camphor (4-MBC), TiO2 and ZnO, are detected in nearshore waters with variable concentrations along the day and mainly concentrated in the surface microlayer (i.e. 53.6-577.5 ng L-1 BZ-3; 51.4-113.4 ng L-1 4-MBC; 6.9-37.6 μg L-1 Ti; 1.0-3.3 μg L-1 Zn). The presence of these compounds in seawater suggests relevant effects on phytoplankton. Indeed, we provide evidences of the negative effect of sunblocks on the growth of the commonly found marine diatom Chaetoceros gracilis (mean EC50 = 125±71 mg L-1). Dissolution of sunscreens in seawater also releases inorganic nutrients (N, P and Si forms) that can fuel algal growth. In particular, PO4 3- is released by these products in notable amounts (up to 17 μmol PO4 3- g-1). We conservatively estimate an increase of up to 100% background PO4 3- concentrations (0.12 μmol L-1 over a background level of 0.06 μmol L-1) in nearshore waters during low water renewal conditions in a populated beach in Majorca island. Our results show that sunscreen products are a significant source of organic and inorganic chemicals that reach the sea with potential ecological consequences on the coastal marine ecosystem. © 2013 Tovar-Sánchez et al.Peer Reviewe