A sustainable and innovative method to determine parabens in body creams for exposure and risk assessment.

Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) are among the most widely used preservatives in cosmetics, drugs, and foods. These compounds have been associated with toxic effects due to the overuse of products with parabens in their formulation. The toxicity of parabens may be correlated to endocrine disruption, owing to their ability to mimic the actions of estradiol. In this paper, a simple, sustainable, robust, and innovative dispersive liquid-liquid microextraction (DLLME) technique was developed and employed to extract these xenobiotics from body cream samples, aiming to calculate the margin of safety (MoS) to assess the risk of exposure. The validated method presented suitable linearity (r > 0.99), lower limits of detection (ranging from 0.01 to 0.04 % w/w), and satisfactory precision and accuracy (ranging from 4.33 to 10.47, and from -14.25 to 13.85, respectively). Seven of the ten analysed samples presented paraben contents within the acceptable concentration according to European legislation. The MoS value obtained for PrP (37.58) suggested its reduced safety, indicating that PrP may significantly contribute to systemic exposure resulting from the use of personal care products.

Magnetic carbon nanotubes modified with proteins and hydrophilic monomers: Cytocompatibility, in-vitro toxicity assays and permeation across biological interfaces.

Carbon nanotubes are promising materials for biomedical applications like delivery systems and tissue scaffolds. In this paper, magnetic carbon nanotubes (M-CNTs) covered with bovine serum albumin (M-CNTs-BSA) or functionalized with hydrophilic monomers (M-CNTs-HL) were synthesized, characterized, and evaluated concerning their interaction with Caco-2 cells. There is no comparison between these two types of functionalization, and this study aimed to verify their influence on the material's interaction with the cells. Different concentrations of the nanotubes were applied to investigate cytotoxicity, cell metabolism, oxidative stress, apoptosis, and capability to cross biomimetic barriers. The materials showed cytocompatibility up to 100 µg mL-1 and a hemolysis rate below 2 %. Nanotubes' suspensions were allowed to permeate Caco-2 monolayers for up to 8 h under the effect of the magnetic field. Magnetic nanoparticles associated with the nanotubes allowed estimation of permeation through the monolayers, with values ranging from 0.50 to 7.19 and 0.27 to 9.30 × 10-3 µg (equivalent to 0.43 to 6.22 and 0.23 to 9.54 × 10-2 % of the initially estimated mass of magnetic nanoparticles) for cells exposed and non-exposed to the magnets, respectively. Together, these results support that the developed materials are promising for applications in biomedical and biotechnological fields.

Magnetic restricted-access carbon nanotubes for SPME to determine cannabinoids in plasma samples by UHPLC-MS/MS.

This manuscript describes the development of magnetic restricted-access carbon nanotubes (M-RACNTs) for use as SPME sorbent to determine cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) in human plasma samples by UHPLC-MS/MS. The adsorptive phase was immobilized on an SPME device by electromagnetic interactions between the M-RACNTs and a cylindrical neodymium magnet (3-mm diameter x 8-mm height) attached to a stainless-steel rod (3-mm diameter x 40-mm height). The M-RACNTs were synthesized by incorporating Fe3O4 magnetic nanoparticles (MNPs) into commercial carbon nanotubes (CNTs); then the surface of the resulting sorbent was further coated with a layer of bovine serum albumin (BSA). Characterization techniques (SEM, FTIR, and Zeta potential) confirmed the presence of both MNPs and BSA layer dispersed through the structure of the CNTs. The M-RACNTs presented adequate sorption capacity, stable physical/chemical characteristics, and appropriate magnetic properties. Protein exclusion capacity (about 98.5%) was attributed to the chemical diffusion barrier created by the BSA network at the outer surface of the sorbent. The SPME parameters (sample pH, equilibrium time, and desorption conditions) were optimized by design of experiments (fraction factorial planning). The method (validated according to the FDA guidelines) presented adequate selectivity and linearity (coefficient of determination higher than 0.99) at concentrations ranging from the lower limit of quantification (LLOQ) (10 ng mL-1) to the upper limit of quantification (ULOQ) (300 ng mL-1) for both CBD and THC. Precision and accuracy varied from 4.47 to 19.84% (LLOQ) and -6.90 to 17.78% (LLOQ), respectively. Carry-over and matrix effect were not significant. The method was successfully applied to determine plasmatic CBD levels in healthy volunteers attending a single session of oral drug administration and THC levels in frequent cannabis smokers.

Online biological sample preparation with restricted access hybrid carbon nanotubes for determination of anti-smoking drugs.

Untreated samples were injected directly into a column switching system, an online SPE technique, using an extraction column packed with restricted access hybrid carbon nanotubes (RAHCNTs), a novel type of restricted access material, in an ultra-high performance liquid chromatography, coupled to a mass spectrometer (UHPLC-MS/MS). The synthesis of used restricted access material was relatively simple, quick, and reproducible, and had a high material yield. Compared to its predecessor, which is covered with bovine serum albumin (Restricted Access Carbon Nanotubes-RACNTs), RAHCNTs have improved performance when used for the analysis of organic compounds. These molecules have a greater adsorption capacity due to the insertion of hydrophilic monomers (tetraethyl orthosilicate (TEOS), 3-(trimethoxysilyl)propyl methacrylate (MPS), glycerol dimethacrylate (GDMA), and hydroxyethyl methacrylate (HEMA)) in the external layer. In addition, the formation of the hybrid material provides greater chemical and thermal stability, supporting wide pH and temperature ranges, and high concentrations of acidic and basic solutions. It also supports high proportions of organic solvents in the medium. Another significant advantage of the material is its longer lifetime, as it can be reused for approximately 500 analytical cycles without any loss of efficiency, versus 300 for RACNTs. In the method developed to determine anti-smoking drugs (varenicline and bupropion) simultaneously, as well as nicotine and some of their metabolites in human blood serum, the RAHCNTs were capable of retaining the analytes efficiently, whereas the macromolecules were excluded (almost 100%). The method was linear for all the determined analytes (coefficients of determination higher than 0.99), with limits of detection and quantification ranging from 0.6 to 2.5 µg L-1 and from 1.0 to 5.0 µg L-1, respectively. High extraction recovery values were obtained (higher than 88%), as well as inter and intra-assay accuracy and precision results that are in accordance with values recommended by the FDA. The method is promising for therapeutic monitoring and new personalized strategies for patients under antismoking treatment, using a small sample volume (100 µL). In addition, RAHCNTs are capable of simultaneously extracting analytes with very different physical-chemical characteristics.

Restricted Access Molecularly Imprinted Polymers.

The use of conventional molecularly imprinted polymers (MIPs) for biological sample preparation is a difficult procedure due to the presence of high concentrations of proteins which can obstruct the selective binding sites, decrease the adsorption capacity, and compromise the analytical validation. In this way, modifications of conventional MIPs have been carried out in order to give them the ability to exclude macromolecules. Superficial coverings with hydrophilic groups and/or proteins have been the main procedures to obtain these restricted access molecularly imprinted polymers (RAMIPs ). These materials have been efficiently used for the selective extraction of small molecules from untreated complex matrices (e.g., blood, plasma, serum, and milk), without the need of a pre-deproteinization step. In this chapter, we describe a generic synthesis protocol to obtain RAMIPs as well as the assays to evaluate the protein exclusion efficiency and possible applications in offline and online procedures.

Magnetic restricted-access carbon nanotubes for dispersive solid phase extraction of organophosphates pesticides from bovine milk samples.

Magnetic restricted-access carbon nanotubes (M-RACNTs) were synthesised and used for dispersive solid phase extraction of organophosphates (chlorpyriphos, malathion, disulfoton, pirimiphos) from commercial bovine raw milk samples. Due to their magnetic susceptibility, M-RACNTs were easily separated from the samples/solvents using a neodymium magnet, and the extracted organophosphates were analysed by gas chromatography-mass spectrometry. The protein exclusion capacity was about 100%. Kinetic and isotherm data (for M-RACNTs - malathion interaction) were adequately adjusted to the pseudo-second order and Sips models, respectively, and the maximum adsorption capacity was about 0.55 mg g-1. The method presented linear ranges from 5.0 to 40.0 µg L-1 for all analytes, with determination coefficients from 0.9902 to 0.9963. The intra-assay precisions (as relative standard deviation) and accuracies (as relative error) ranged from 10.47 to 19.85% and from -0.18 to -18.80%, respectively, whereas the inter-assay precisions ranged from 6.48 to 18.76% and from -0.22 to 19.49%, respectively for 5.0, 20.0 and 40.0 µg L-1 organophosphates levels. The organophosphates were not stable at 4 and 24 h (relative errors ranged from -39.30 to 72.07% and -69.64 to 75.95%, respectively). Limits of detection ranged from 0.36 to 0.95 µg L-1, and 5 µg L-1 was defined as the limit of quantification for all the analytes. The proposed method was applied in the determination of organophosphates in five commercial milk samples, and no pesticides were detected.

Biological sample preparation by using restricted-access nanoparticles prepared from bovine serum albumin: application to liquid chromatographic determination of ß-blockers.

Restricted-access nanoparticles (RANPs) were prepared from bovine serum albumin by coacervation. They have an average sized of 311 nm. They were characterized and used to capture the ß-blockers atenolol, metoprolol and propranolol from untreated biological samples. It is shown that both high protein affinity drugs (propranolol) and low protein affinity drugs (atenolol) could be rapidly extracted from plasma. This is revealed by kinetic and isothermal adsorption studies. On the other hand, almost all proteins from the sample were excluded. This demonstrates the efficiency of RANPs as restricted-access material. Sample preparation was carried out by solid phase microextraction using a probe obtained by the fixation of the RANPs at the end of a glass capillary. Atenolol (in concentrations from 100 to 1200 µg L-1), metoprolol (from 80 to 1000 µg L-1) and propranolol (from 15 to 200 µg L-1) were extracted from spiked plasma samples and analyzed by LC MS/MS without using a separation column. Correlation coefficients >0.99, good precision, accuracy, robustness, and lack of memory effects were observed for all of the analytes. The detection limits (at an S/N of 3) are 25.6, 14.6, and 3.8 µg L-1 for atenolol, metoprolol and propranolol, respectively. Ten samples can be simultaneously extracted within ∼15 min. Plasma samples of patients undergoing medical treatment were successfully analyzed with the method. Graphical abstract Schematic representation of a bovine serum albumin-based restricted access nanoparticle that exclude proteins from a human plasma sample but capture the small analytes.

Direct extraction of tetracyclines from bovine milk using restricted access carbon nanotubes in a column switching liquid chromatography system.

This paper describes, for the first time, the use of restricted access carbon nanotubes (RACNTs) in the analysis of tetracyclines from milk samples, in a multidimensional liquid chromatographic system. Milk samples were initially acidified and centrifuged, and then the supernatant was directly analyzed in a column switching system in backflush configuration employing an extraction column of RACNTs. The sorbent was able to exclude all the remained proteins in less than 2.0min. The method was linear from 50 to 200µgL-1 and the coefficients of determination (r2) were 0.997, 0.992, 0.994 and 0.998 for oxytetracycline (OXI), tetracycline (TC), chlortetracycline (CTC) and doxycycline (DOX), respectively. The analytical range included the maximum residue limits established by the regulatory agency.