The presence of N-nitrosamines - potentially carcinogenic compounds - is being reported for more than 50 years in pharmaceutical products. However, it only gained notorious prominence in 2018, when regulatory agencies became aware of the presence of N-nitrosodimethylamine in angiotensin II receptor antagonists, drugs that are known as sartans. It did not take long for N-nitrosamine impurities to be identified in other medicines, alerting government agencies and pharmaceutical industries to evaluate and control these impurities in their products to mitigate the risk. The sources of contamination can be numerous, including the use of contaminated raw material, formation in the synthesis of active pharmaceutical ingredients or during storage, the water used in the process, and the packaging material. This review article presents the timeline of the presence of N-nitrosamines in consuming products, toxicological aspects, legislation, and analytical methods. It provides relevant information on possible sources of contamination in the production and storage process that may explain the presence of these compounds considered a cohort of concern in pharmaceuticals.

Fluoroquinolones antimicrobials are partially excreted in natura after administration. Their occurrence was investigated in hospital raw sewage (HRS) and treated wastewater (TW) using an online solid phase extraction-ultra high-performance liquid chromatography-tandem mass spectrometry method (SPE-UHPLC-MS/MS). The analytical curves ranged from 0.25 to 46 ng mL-1 and the matrix effect, assessed for marbofloxacin and lomefloxacin, ranged from –63 to +1%. All HRS samples contained ciprofloxacin (1-34 ng mL-1) and ofloxacin (0.9-27 ng mL-1), while norfloxacin was detected in 17% of the samples (0.8-4.4 ng mL-1). Only ciprofloxacin (0.5-5.6 ng mL-1) was detected in TW samples. The antimicrobial activity of the HRS samples for E. coli was higher than a ciprofloxacin solution of 1 mg L-1, due to the presence of other antimicrobial agents. Ozonation (10 mg O3 L-1 min-1 ; 10 min) degraded up to 84% of the fluoroquinolones and removed the antimicrobial activity of HRS samples.

Synthetic fungicides are a common treatment for post-harvest diseases in fruits, although demand is increasing for alternatives such as biopesticides. The aim of this work was to investigate the presence of naturally occurring antifungal compounds in Brazilian specimens of the weed Conyza canadensis. Two compounds [(4Z)-lachnophyllum lactone and (4Z,8Z)-matricaria lactone] were isolated and their antifungal activities were evaluated against eight postharvest disease fungi. Aspergillus niger, Cladosporium sp., and Penicillium digitatum proved susceptible to the treatment (minimum inhibitory concentrations varying from 32 to 64 µg mL-1). These fungi are common postharvest pathogens of fruits and vegetables, causing rots and secreting mycotoxins. A green and sustainable extraction method employing pressurized hot water was developed and optimized (100 °C, 4 × 1 min cycles). Yields of 1.46 and 0.24 mg g-1 were obtained for (4Z)-lachnophyllum lactone and (4Z,8Z)-matricaria lactone, respectively. The extract could be applied directly to fruits and vegetables in postharvest treatments.

Sulfonamides are among the most widely employed antibacterial in veterinary medicine. Because a substantial proportion of sulfonamides are excreted unchanged as parent compounds after administration or are excreted as their metabolites through urine and feces, their presence in soils is a matter of concern. Adsorption and desorption are important processes that influence the transport, transformation and bioavailability of antimicrobials in soils, and data related to sorption capacity are therefore needed for environmental risk assessments. The sorption potential of sulfachloropyridazine (SCP) was assessed in four Brazilians soils using batch equilibrium experiments. The adsorption/desorption data fit well Freundlich isotherms. The sorption coefficients (KD) ranged from 1.00 to 4.48 cm3 g-1, and the Freundlich adsorption coefficient (KF) ranged from 1.89 to 5.63 µg1-1/n (cm3)1/n g-1 showing that SCP adsorption is generally low in the studied soils. The results were compared with previously published data obtained for the sorption of other sulfonamides in the same four soils.

A molecularly imprinted polymer (MIP) for the diuretic drug hydrochlorothiazide (HCTZ) based on theoretical predictions was developed. Molecular modeling calculations were performed to study the intermolecular interactions in the pre-polymerization mixture and to select a suitable functional monomer and a porogenic solvent for the synthesis of the MIP. To confirm the results of the theoretical predictions, three MIPs were synthesized and evaluated using the equilibrium batch rebinding method. A water-compatible MIP was prepared using HCTZ as the template and acrylamide as the functional monomer (FM) with ethylene glycol dimethacrylate as the cross-linker and tetrahydrofuran as the porogen. An imprinting factor of 8.24 was obtained. The polymer was characterized by Fourier transform infrared (FTIR), solid-state nuclear magnetic resonance, scanning electron microscopy, thermogravimetric analysis and nitrogen sorption porosimetry. In addition to HCTZ, six structurally related compounds were tested to evaluate the selectivity of the HCTZ-MIP, and cross-selectivity of the MIP was verified.

<p>Recently, the Brazilian Ministry of Agriculture, Livestock and Supply (MAPA) published a validation and analytical quality control guide called the “Guia de Validação e Controle de Qualidade Analítica – Fármacos em Produtos para Alimentação Animal e Medicamentos Veterinários”, in order to guide officers and accredited laboratories in the validation of analytical methods for the quality control of veterinary medicines, drug contaminants in feed and depletion studies (residues of drugs in biological matrices). The aim of this study was to present a critical evaluation of the concepts and procedures defined in this document. The Guide was applied for the validation of chromatographic methods intended to be used for the quantification of antimicrobial and antiparasitic drugs in veterinary medicines. Methods for the determination of ivermectin, abamectin, sulfadiazine, sulfadimethoxine, sulfaquinoxaline, streptomycin, dihydrostreptomycin and florfenicol were validated using the Guide. Each validation parameter was evaluated and discussed. A total of 55 samples of veterinary drugs were analyzed.</p>

Electric field-assisted solid phase extraction using syringe type cartridges (E-SPE) is a recent approach with a high capacity to obtain differential selectivity and/or recovery in comparison with conventional solid phase extraction (SPE). In this work, E-SPE was employed for the extraction of the anionic dye sunset yellow. During the washing step the electric field was evaluated with the top electrode negatively (E-SPE(–/+)) or positively charged (E-SPE(+/–)) and the results were compared with conventional SPE to understand how the electrochromatographic parameters can influence the recovery of the dye. Using the E-SPE(–/+) the electric field can increase the elution of the dye from the cartridge by over 57-fold. This notable result can be attributed to the electrophoretic velocity of the dye in the direction of the flow rate of the eluent. These results demonstrated that E-SPE is an interesting approach to elute ionic compounds with reduced volumes of eluent or less amount of organic solvent.

A qualidade dos sítios de reconhecimento molecularmente impressos dependem dos mecanismos e da extensão das interações monômero funcional-molde presentes na mistura de pré-polimerização. Assim, a compreensão dos parâmetros físicos que governam estas interações é a chave para a produção de um polímero de impressão molecular (MIP) altamente seletivo. Neste trabalho, novos estudos de modelagem molecular foram realizados para otimizar as condições de impressão molecular de fenitrotiona. Foram avaliados quatro possíveis monômeros funcionais. Cinco solventes porogênicos foram investigados utilizando o método da polarização contínua. O MIP baseado em ácido metacrílico (MAA-MIP) sintetizado na presença de tolueno demonstrou ser o complexo mais termodinamicamente estável. Ao contrário, MIP com base em ácido p-vinilbenzóico (PVB-MIP) teve a menor energia de ligação. De acordo com os parâmetros de adsorção ajustados pela isoterma de Langmuir-Freundlich, MIP-MAA apresentou duas vezes o número de sítios de ligação em comparação com o PVB-MIP (103,35 e 53,77 µmol g-1, respectivamente).

The quality of molecularly imprinted recognition sites depend on the mechanisms and the extent of the functional monomer-template interactions present in the prepolymerization mixture. Thus, an understanding of the physical parameters governing these interactions is key for producing a highly selective molecularly imprinted polymer (MIP). In this paper, novel molecular modeling studies were performed to optimize the conditions for the molecular imprinting of fenitrothion. Four possible functional monomers were evaluated. Five porogenic solvents were investigated employing the polarizable continuum method. The MIP based in methacrylic acid (MAA-MIP) synthesized in the presence of toluene shown to be the most thermodynamically stable complex. Contrarily, MIP based in p-vinylbenzoic acid (PVB-MIP) had the lowest binding energy. According to the adsorption parameters fitted by the Langmuir-Freundlich isotherm, MAA-MIP presented twice the number of binding sites compared to PVB-MIP (103.35 and 53.77 µmol g-1, respectively).

O desenvolvimento de um método QuEChERS-HPLC-DAD usando uma coluna Lichrospher RP-60 Select B (250 x 4,6 mm x 5 µm) a 40 ºC, fase móvel constituída por tampão de fosfato: acetonitrila (75:25, v/v) a uma vazão inicial de 0,5 mL min-1, aumentando 1,2 mL min-1 e a 265 nm é apresentado para a determinação simultânea de sulfadiazina, sulfametoxipiridazina e sulfametoxazol em amostras de peito de frango. O QuEChERS é barato, rápido e fácil, e a extração dos analitos da matriz foi empregada com sucesso. Além disso, o método apresentou linearidade, na faixa de 25, 50, 100, 150, 175 e 200 µg kg-1, precisão, seletividade e sensibilidade. A precisão intradia (RSD %) para o método QuEChERS foi entre 3,6-10,8 (SDZ), 6,9-14,1 (SPZ) e 1,9-10,9 (SMX) e a precisão interdias (RSD%) foi entre 1,5-9,7, 1,7-4,1 e 2,1-10,1, respectivamente. Resultados de exatidão (tendenciosidade) foram na faixa de -8,6 a +11,9%. Portanto, o método validado é útil para a monitorização de resíduos de medicamentos avaliados em amostras de frangos, bem como todos os valores estavam dentro dos critérios aceitáveis utilizados para a segurança dos alimentos. De seis amostras analisadas, nenhuma apresentou contaminação de sulfonamidas nos níveis detectáveis estudados.

The development of a QuEChERS-HPLC-DAD method using a Lichrospher 60 RP-Select B column (250 x 4.6 mm x 5 µm) at 40ºC, mobile phase constituted by phosphate buffer:acetonitrile (75:25, v/v) at a initial flow rate of 0.5 mL min-1, increased by 1.2 mL min-1 and at 265 nm is presented for simultaneous determination of sulphadiazine, sulphametoxipiridazine and sulphamethoxazole in chicken breast samples. QuEchERS is inexpensive, fast and easy, and the extraction of the analytes of the matrix was successfully employed. In addition, the method presented linearity, in the range of 25, 50, 100, 150, 175, and 200 µg kg-1, precision, selectivity and sensitivity. The intraday precision (RSD %) for QuEChERS method was between 3.6-10.8 (SDZ), 6.9-14.1 (SPZ) and 1.9-10.9 (SMX) and interday precision (RSD%) was between 1.5-9.7, 1.7-4.1 and 2.1-10.2, respectively. Results of accuracy (bias) were in the range of -8.6 to +11.9 %. Therefore, the validated method is clearly useful for the practical residue monitoring of the drugs evaluated in chicken samples, as all the values were within the acceptable criteria used for food safety. Of 6 samples analyzed, none of them showed contamination of the sulphonamides studied at detectable levels.

Antimicrobials, among other veterinary drugs, are used worldwide in industry and agriculture to protect animal health and prevent economic loss. In recent years, they have been detected in various environmental compartments, including soil, surface and groundwater and have become a topic of research interest. Emphasizing this class of compounds, this review presents the different pathways which veterinary drugs enter in the environment, in particular contaminate soils. Also are presented regulatory aspects and guidelines, adsorption/desorption and degradation of these compounds in soils and the consequences of its dispersal in the environment.

N-nitrosamines are carcinogenic compounds that have been found during the last three decades in a variety of consumer products, including cosmetic and personal care products, and their raw materials. These compounds are formed from amine precursors and nitrosating agents present in the formulations. This paper reviews the formation and occurrence of N-nitrosamines in cosmetic products, as well as presents considerations about analytical, toxicological and regulatory aspects.

Different agencies that supply validation guidelines worldwide establish almost the same parameters to be evaluated in the validation process of bioanalytical methods. However, they recommend different procedures, as well as establish different acceptance criteria. The present review delineates and discusses the stages involved in the validation procedures of bioanalytical methods designed for determining veterinary residues in food, explaining the main differences in the guidelines established for this purpose by the main regulatory agencies in the world.

The electrochemical behavior of N-nitrosothiazolidine carboxylic acid (NTAC) on gold and hanging mercury electrodes, using the cyclic and square wave voltammetries, was studied. Whereas NTAC suffer reduction in a single step on the mercury electrode, two peaks appears on the cyclic voltammograms on the gold electrode, one anodic peak overlaying the gold oxide process at 1.2 V and one cathodic peak at -0.41 V vs Ag/AgCl, KCl 3.0 mol L-1. The cathodic peak depends on the previous oxidation of NTAC at the electrode surface, presents irreversible and adsorption controlled characteristics and it is suitable for quantitative purposes.

Neste trabalho foi desenvolvido um método para a determinação de hexaclorobenzeno, lindano, heptaclor, heptaclor epóxido, aldrin, dieldrin, endrin, DDT e DDE em folhas de Mikania laevigata, Maytenus ilicifolia e Cordia verbenacea, empregando a Cromatografia Gasosa acoplada a Espectrometria de Massas (GC-MS). A extração dos pesticidas foi realizada por extração sólido-líquido (SLE), seguida de limpeza por extração em fase sólida (Florisil e silica-gel). A quantificação foi realizada usando o GC-MS no modo SIM. A recuperação média variou de 70 a 124%. A precisão inter-ensaio de uma amostra fortificada com 200 ng g-1 de cada pesticida variou de 1,0 a 7,3%. Os limites de quantificação variaram de 3,0 a 30 ng g-1 e estão abaixo dos limites máximos de resíduos (MLR) estabelecidos para os pesticidas sob estudo. O método foi empregado para analisar amostras de Mikania laevigata, Maytenus ilicifolia e Cordia verbenacea de um campo experimental de Paulínia, SP, Brasil. As amostras apresentaram contaminação com dieldrin acima do MRL estabelecido pela Farmacopéia Européia (50 ng g-1).

A method using Gas Chromatography coupled to Mass Spectrometry (GC-MS) for the determination of hexachlorobenzene, lindane, heptachlor, heptachlor epoxide, aldrin, dieldrin, endrin, 4,4'-DDT and 4,4'-DDE in leaves of Mikania laevigata, Maytenus ilicifolia and Cordia verbenacea was developed. Extraction of the pesticides was carried out by solid-liquid extraction (SLE), followed by clean-up in solid phase mixed cartridge (Florisil and silica-gel). Quantification was performed using GC-MS in the selected ion monitoring mode. Mean recovery rates of 70 to 124% were obtained. The inter-assay precision of a sample fortified with 200 ng g-1 of each pesticide was in the range of 1.0 to 7.3%. The quantitation limits ranged from 3.0 to 30 ng g-1 and were below the Maximum Residue Limit (MRL) for all the pesticides under study. The method was employed to analyze samples of Mikania laevigata, Maytenus ilicifolia and Cordia verbenacea from an experimental field in Paulínia, SP, Brazil. The samples presented contamination with dieldrin above the MRL established by the European Pharmacopoeia (50 ng g-1).

Foi estabelecido um método cromatográfico rápido e simples para a determinação de riboflavina em leite bovino, na presença de tetraciclinas. Para tanto, as proteínas foram precipitadas com ácido tricloroacético e a separação realizada por CLAE em fase reversa com detector de fluorescência. Foi utilizada uma coluna C8 com eluição isocrática e fase móvel acetato de sódio 0,1 mol L-1, cloreto de cálcio 35 mmol L-1, EDTA 25 mmol L-1: metanol (65:35 v/v). O método foi validado mediante avaliação dos seguintes parâmetros: linearidade (0,9980), faixa linear (0,50 a 1,30 µg mL-1), precisão intra e inter-ensaio (RSD < 0,5%), exatidão (recuperação 92%) e limites de detecção e de quantificação (0,75 µg mL-1 e 0,22 µg mL-1, respectivamente). O método foi aplicado na análise de leite integral e desnatado, mostrando-se robusto na presença de substâncias fluorescentes como as tetraciclinas, e quando comparado com o método espectrofluorimétrico, não revelou diferença significativa (p < 0,05) entre os resultados obtidos.

An easy and simple chromatographic method for the determination of riboflavin in bovine milk in the presence of tetracyclines was established. For this, the proteins were precipitated with trichloroacetic acid and the separation was carried out by reversed-phase HPLC with fluorescence detection. A C8 column was used with isocratic flow using a mobile phase consisting of 0.1 mol L-1 sodium acetate, 35 mmol L-1calcium chloride and 25 mmol L-1 EDTA : methanol (65:35 v/v). The method was validated by means of the following parameters: linearity (0.9980), linear range (0.50 - 1.30 µg mL-1), intra- and inter-assay precision (RSD < 0.5%), accuracy (recovery 92%), and detection and quantitation limits (0.75 µg mL-1 and 0.22 µg mL-1, respectively). The method was applied for analysis of full cream and skimmed milk, showing robustness in the presence of tetracyclines, and when compared with a spectrofluorimetric method showed no significant difference (p < 0.05) between the results obtained.