Biomonitoring and risk assessment of human exposure to triazole fungicides.

Risk assessment and biomarkers were evaluated in volunteers exposed to triazole fungicides in southern Minas Gerais, Brazil. Volunteers were divided into two groups: occupationally and environmentally exposed to pesticides (n = 140) and those unexposed (n = 50) from urban areas. Urine samples were analyzed by GC-MS for triazoles, and samples from men and women in the exposed group were quantified. Groups were further stratified by sex to evaluate the biomarkers results. Oxidative stress was indicated by biomarker analysis for occupationally exposed men with elevated malondialdehyde levels and reduced superoxide dismutase and catalase activity (p < 0.0001). Bile acid levels were also elevated in the exposed group (p < 0.0001). Biomarkers in this study suggest recent, reversible changes due to pesticide exposure. Liver enzyme levels showed no significant differences. The highest Estimated Daily Intake for epoxiconazole ranged from 0.534 to 6.31 µg/kg-bw/day for men and 0.657-8.77 µg/kg-bw/day for women in the exposed group. Considering the highest detected urinary triazole value, the calculated Hazard Quotient for epoxiconazole was 0.789 for men and 1.1 for women. Results indicate a health risk associated with environmental triazole exposure, highlighting the importance of biomonitoring in risk assessment to prevent intoxication and assist in mitigating adverse health effects from chronic pesticide exposure.

Assessment of cellular damage with cytome assay among environmental/occupational triazole.

The use of triazole fungicides is common in Minas Gerais, Brazil. However, the risk arising from excessive and often unprotected exposure can be harmful to farmers. Therefore, we evaluated volunteers, exposed to triazole fungicides for cellular damage caused by this pesticide. In the buccal micronucleus cytome assay (BMCyt), cells were analyzed. Urinary triazoles were analyzed by the Liquid-Liquid Extraction coupled with Gas-chromatography/mass-spectrometry (LLE-GC/MS). Statistical differences were found for all cell types evaluated in residents of rural areas (n = 145). Analysis of variance showed statistical difference in kariolytic and pyknotic cells, between the groups of men and women living in rural areas, with higher incidence in the male group. Likewise, higher concentrations triazoles in urine samples in the male group were observed. Greater cellular damage suggests increases in DNA damage, chromossomal instability and cell deaths. The results showed the urgency of the public management with the implementation of measures to minimize the pesticides exposure.

Evaluation of the nicotine metabolite ratio in smoking patients treated with varenicline and bupropion.

Background: Smoking is the leading cause of preventable death worldwide. It is responsible for several types of cancer, cardiovascular diseases, and diseases of the reproductive system, among others. Therefore, advances in research are increasingly necessary in order to make smoking cessation treatment more effective. Some studies have investigated the association of the nicotine metabolite ratio (NMR) with general characteristics and treatment outcomes. In the present study, the main aim was to evaluate the NMR in smoking patients from an Assistance Program of a tertiary cardiology hospital. Methodology: Serum samples were collected from 185 patients at T0 (while patients were still smoking and before starting pharmacological treatment). Cotinine and hydroxycotinine analytes were measured using liquid-chromatography tandem mass-spectrometry (LC-MS/MS). By looking at the relationship between hydroxycotinine and cotinine, we can obtain the NMR, with which it is possible to classify patients into slow metabolizers (NMR < 0.31), as well as normal or fast metabolizers (NMR ≥ 0.31). Results: From 185 patients, 55 were considered slow metabolizers and 130 as normal/fast. The metabolite averages were associated with the number of cigarettes smoked per day (p < 0.001 for cotinine and 0.023 hydroxycotinine). However, we were unable to analyze the association of the NMR with general and clinical characteristics of patients under smoking cessation treatment. Conclusion: We were able to evaluate the NMR, and to observe categories of metabolizers in Brazilian patients under pharmacological treatments. Thus, this study can contribute to the indication of a form of analysis, which might form part of the customization of smoking cessation treatments and, consequently, improve the success rates.

Online restricted access molecularly imprinted solid-phase extraction coupled with liquid chromatography-mass spectrometry for the selective determination of serum bile acids.

A rapid and sensitive online restricted access molecularly imprinted solid-phase extraction method coupled to a liquid chromatography-mass spectrometry (LC-MS) system for simultaneous determination of serum bile acids as well as their taurine and glycine conjugates was developed. Reversible liver damage of workers exposed to volatile organic solvents can be investigated based on the level of the analyzed molecules. A restricted access molecularly imprinted polymer coated with bovine serum albumin (RAMIP-BSA) was synthesized and used as the extraction phase. The column switching liquid chromatography system was able to exclude about 100% of the macromolecules and extract/separate nine bile acids from blood human serum samples, in a total time of 40 minutes. The developed method was validated based on the Food and Drug Administration (FDA) guidelines, being linear for all the analytes in their respective analytical ranges (coefficients of determination higher than 0.99), with limits of detection (LOD) and quantification (LOQ) ranging from 2.0 to 5.7 µg L-1 and from 10.0 to 25.0 µg L-1, respectively. Suitable results for precision (relative standard deviation ranged from 3.2 to 14.5% and 0.7 to 14.8%, respectively for intra and inter-assay) and accuracy (relative error ranged from -14.8 to 14.2%; -13.8 to 14.3%) were obtained. The validated analytical method was applied to determine bile acids in serum samples of five workers occupationally exposed to volatile organic solvent, demonstrating its applicability in the assessment of these toxicants.

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.

Multivariate Optimization of an SPME Technique for GC-MS Analysis of Urinary BTX.

Volatile organic compounds (VOCs), such as benzene, toluene and xylenes (BTX), are recognized as environmental contaminants due to their acute and chronic toxic effects, and toluene is a substance contained in products used in inhalants. In this way, methods able to determine these substances in non-invasive matrices offer great applicability for assessing acute exposure. In this study, a functionalized polymer, chloropropyltrimethoxysilane/polydimethylsiloxane, was evaluated as a potential material to be used in solid-phase microextraction for the quantification of BTX in urine by gas chromatography coupled to mass spectrometry (GC-MS). The method optimization was performed by using fractional factorial planning 2 (4-1) and the Doehlert's experiment. Desorption time and salinity were the most important factors that impact the sensitivity of the method. Spectroscopic and thermogravimetric characterization demonstrated the functionalization of the material and its thermal stability up to 390°C. This allowed it to be used for ~60 analytical cycles without loss of efficiency. The proposed method demonstrated a satisfactory analytical performance to determine the VOCs studied. The protocol agrees with the principles of green analytical chemistry since the procedure reduced the reagents consumed and wastes generated. It represents a promising tool for acute exposure assessment to BTX since urine tests demonstrated its applicability.

Interchangeability among carbamazepine formulations: the impact over epilepsy patients

Abstract The treatment of epilepsy is complex and a matter of concern is the interchangeability among different formulations available for antiepileptic drugs. To evaluate the effects of interchangeability among carbamazepine formulations on patients with epilepsy. This is a prospective cohort study that included adult outpatients diagnosed with epilepsy and under pharmacological treatment with carbamazepine. Before switching the brand/manufacturer, the "Interchangeable Pharmaceutical Product in the Treatment of Epilepsies" questionnaire was applied. The questionnaires "Adverse Events Profile" and Quality of Life in Epilepsy-31, so as the plasma carbamazepine concentrations, were evaluated before and after the brand/ manufacturer switch. Physical-chemical tests aiming to assess tablets quality were performed in accordance with the Brazilian Pharmacopoeia 5th edition. The study population was composed by 14 patients (mean age: 44.6 years), with 10 of females. From those interviewed, 10 had no knowledge about the three antiepileptic drugs formulations available. The frequency of adverse event "problems with skin" incresead (p=0.023) and "upset stomach" decreased (p=0.041) after the changeover. The adverse events profile was associated with only two quality of life domains: "energy/fatigue" (p=0.048) and "total score" (p=0.018). Divergent results between generic and reference formulations were observed in purity-water test (reference: 1.96%, generic: 4.84%) and dissolution test, in which the generic formulation presented 66.27 to 85.77% of carbamazepine dissolved after the third level. Conclusions: Objective differences before and after the brand/manufacturer switch were not observed, in spite of patients' perceptions. Despite that, more studies in the field are necessary, especially on the interchangeability among generic antiepileptics, in order to better elucidate switching consequences on patients' life.

Endpoints as human biomarkers in exposure assessment of triazoles fungicides.

Potential endpoint biomarkers were evaluated in the assessment of exposure to triazoles, in the southern region of Minas Gerais, Brazil. Volunteers were divided into three groups: occupationally exposed and rural residents (n = 21), non-occupationally exposed and rural residents (n = 35) and non-occupationally exposed and urban residents (n = 30). Of all endpoints evaluated, plasma concentration of androstenedione (p < 0.001) and glycine-conjugated bile acids presented statistical differences in the three studied groups (p < 0.05). However, our findings concerning oxidative stress and testosterone levels, plus that related to unconjugated and taurine conjugated bile acids, suggested that more studies are necessary to evaluate their potential as biomarkers for triazole exposure, as statistical significance was not attained between the groups. Our human population data contributes to the development of triazole exposure risk assessment with respect to these potential effect biomarkers, in potentially vulnerable groups and individuals.

Toxicological analyses: analytical method validation for prevention or diagnosis.

The need for reliable results in Toxicological Analysis is recognized and required worldwide. The analytical validation ensures that a method will provide trustworthy information about a particular sample when applied in accordance with a predefined protocol, being able to determine a specific analyte at a distinct concentration range for a well-defined purpose. The driving force for developing method validation for bioanalytical projects comes from the regulatory agencies. Thus, the approach of this work is to present theoretical and practical aspects of method validation based on the analysis objective, whether for prevention or diagnosis. Although various legislative bodies accept differing interpretations of requirements for validation, the process for applying validation criteria should be adaptable for each scientific intent or analytical purpose.

Assessment of Primary Health Care for rural workers exposed to pesticides.

OBJECTIVE: To evaluate the attributes of Primary Health Care (PHC) for rural workers; to analyze sociodemographic conditions, history of poisoning and hospitalizations for pesticides and use of personal protective equipment; and to verify exposure to pesticides by determining bioindicators. METHODS: Cross-sectional, descriptive-analytical study with a sample of 1,027 rural workers living in municipalities belonging to a regional health department in Southern Minas Gerais, whose PHC is governed by the Family Health Strategy model. We used the adult version of the Primary Care Assessment Tool (PCATool Brazil) and a structured questionnaire to collect socioeconomic data, history of poisoning and hospitalization for pesticides and use of personal protective equipment. Blood samples were collected to measure biomarkers of pesticide exposure and signs of renal and hepatic sequelae. RESULTS: Low education was prevalent, as well as the intense contact of workers with pesticides. Frequent use of personal protective equipment was higher among men, as was the history of poisoning and hospitalizations for pesticides. Rates of 20% poisoning, 15% liver disease and 2% nephropathy were detected. Signs of hepatotoxicity were more frequent in men. Gender differences were all statistically significant. Regarding PHC, only the attribute "degree of affiliation" had a high score. None of the poisoning cases detected in the study were previously diagnosed. CONCLUSIONS: Despite the high coverage of the Family Health Strategy, occupational risk and its consequences have not been detected by health services, which do not seem oriented to primary care, even lacking their essential attributes. There is a need for immediate and effective adaptation of public policies regarding the health of rural workers, with adequate training of teams and review of the portfolio of PHC services offered.

Serum analysis in women and in vitro skin assay for the assessment of exposure to parabens in antiperspirants.

The present study assessed the exposure to methylparaben (MP) and propylparaben (PP) from antiperspirants in serum of 24 women aged 20-30 years old and an in vitro skin assay. An effective liquid chromatography-tandem mass spectrometry method for the determination of MP and PP levels in serum was developed and validated in the range of 10-100 µg/L; the method was fast, simple, sensitive, linear, precise, and accurate. In addition, a simple and rapid liquid chromatography-ultraviolet detection method for the determination of MP and PP levels in antiperspirants was developed and validated in the range of 2-26 mg/L, which presented satisfactory linearity, precision, and accuracy. Using these two methods, 20 commercial antiperspirants were evaluated, and only three showed MP and PP in the formulation. The antiperspirant containing 0.2% and 0.1% w/w MP and PP, respectively, was given to the volunteers, to estimate the internal dose, and submitted to a pig ear skin permeation assay in Franz diffusion cells, presenting a permeation flux of 32% for MP and 71% for PP. In this assay, both MP and PP permeated the skin; however, there was no correlation between antiperspirant use and paraben serum concentration in the volunteers. Graphical abstract.

Assessment of Primary Health Care for rural workers exposed to pesticides / Avaliação da atenção primária à saúde de trabalhadores rurais expostos a praguicidas

ABSTRACT OBJECTIVE To evaluate the attributes of Primary Health Care (PHC) for rural workers; to analyze sociodemographic conditions, history of poisoning and hospitalizations for pesticides and use of personal protective equipment; and to verify exposure to pesticides by determining bioindicators. METHODS Cross-sectional, descriptive-analytical study with a sample of 1,027 rural workers living in municipalities belonging to a regional health department in Southern Minas Gerais, whose PHC is governed by the Family Health Strategy model. We used the adult version of the Primary Care Assessment Tool (PCATool Brazil) and a structured questionnaire to collect socioeconomic data, history of poisoning and hospitalization for pesticides and use of personal protective equipment. Blood samples were collected to measure biomarkers of pesticide exposure and signs of renal and hepatic sequelae. RESULTS Low education was prevalent, as well as the intense contact of workers with pesticides. Frequent use of personal protective equipment was higher among men, as was the history of poisoning and hospitalizations for pesticides. Rates of 20% poisoning, 15% liver disease and 2% nephropathy were detected. Signs of hepatotoxicity were more frequent in men. Gender differences were all statistically significant. Regarding PHC, only the attribute "degree of affiliation" had a high score. None of the poisoning cases detected in the study were previously diagnosed. CONCLUSIONS Despite the high coverage of the Family Health Strategy, occupational risk and its consequences have not been detected by health services, which do not seem oriented to primary care, even lacking their essential attributes. There is a need for immediate and effective adaptation of public policies regarding the health of rural workers, with adequate training of teams and review of the portfolio of PHC services offered.

ABSTRACT OBJETIVO Avaliar os atributos da atenção primária à saúde (APS) na assistência à saúde de trabalhadores rurais; analisar condições sociodemográficas, histórico de intoxicação e internações por agrotóxicos e uso de equipamentos de proteção individual; e verificar a exposição aos praguicidas pela determinação de bioindicadores. MÉTODOS Estudo transversal, descritivo-analítico, com amostra de 1.027 trabalhadores rurais residentes em municípios pertencentes a uma superintendência regional de saúde do sul de Minas Gerais, cuja APS é regida pelo modelo da Estratégia Saúde da Família. Utilizou-se o Instrumento de Avaliação da Atenção Primária (PCATool Brasil) versão adulto e um questionário estruturado para coleta de dados socioeconômicos, histórico de intoxicação e internação por agrotóxicos e uso de equipamentos de proteção individual. Foram coletadas amostras sanguíneas para dosagem de biomarcadores de exposição a praguicidas e de sinais de sequelas renais e hepáticas. RESULTADOS A baixa escolaridade foi prevalente, bem como o contato intenso dos trabalhadores com praguicidas. O uso frequente de equipamentos de proteção individual foi maior entre os homens, assim como o histórico de intoxicação e de internações por agrotóxicos. Detectaram-se índices de 20% de intoxicação, 15% de hepatopatia e 2% de nefropatia. Os sinais de hepatotoxicidade foram mais frequentes em homens. As diferenças entre sexos foram todas estatisticamente significantes. Com relação à APS, apenas o atributo "grau de afiliação" apresentou escore elevado. Nenhum dos casos de intoxicação detectados no estudo tinha diagnóstico prévio. CONCLUSÕES A despeito de uma alta cobertura da Estratégia Saúde da Família, o risco ocupacional e suas consequências não têm sido detectados pelos serviços de saúde, que se apresentam como não orientados à atenção primária, carecendo mesmo de seus atributos essenciais. Percebe-se a necessidade de adequação imediata e efetiva das políticas públicas no que concerne à saúde do trabalhador rural, com adequada capacitação das equipes e revisão da carteira de serviços da APS ofertados.

A sensitive and accurate vortex-assisted liquid-liquid microextraction-gas chromatography-mass spectrometry method for urinary triazoles.

The development and validation of an innovative, simple, rapid, selective and sensitive vortex-assisted liquid-liquid microextraction-gas chromatography- mass spectrometry (VALLME-GC/MS) method to seven triazole fungicides in urine is reported. The confidence parameters were exhaustive evaluated and linearity (r > 0.99), precision (below 15%, to quality controls, and 20%, to lower limit of quantification), accuracy and robustness were adequate for the analysis of cyproconazole, epoxiconazole, metconazole, tebuconazole, triadimenol, propiconazole and triadimefon. To assess the applicability of the method, analyses were performed in volunteers exposed to triazoles in the last 30 days. The method demonstrated satisfactory analytical performance, with sufficient detectability to be applied as a potential tool to biomonitoring individuals exposed to the seven evaluated fungicides.

Risk assessment of the occurrence of aflatoxin and fungi in peanuts and cashew nuts

In the present study, the occurrence of fungi and aflatoxins (AFs) in peanut and cashew nut samples was investigated. Mycological analysis revealed the presence of fungi in 58.8% of samples, and assessment of AFs by chromatographic methods revealed that 52.9% were contaminated by AFs. AFB1 was the principal component in all AF-contaminated samples, with a mean level of 14.0, and 1.08 µg/kg in peanut and cashew nut, respectively. Eleven samples (32.4%) exceeded the total AF maximum level (4 µg/kg) and 8 samples (23.5%) exceeded the AFB1 (2 µg/kg) established by the European Commission. Our findings suggest that the incidence of AFs emphasizes the need for regular monitoring and a more stringent food safety system to control AFs at the lowest possible levels in peanuts and cashew nuts. The hypothetical dietary exposure suggests that the food products evaluated may significantly contribute to the overall human exposure

Risk assessment of occupational pesticide exposure: Use of endpoints and surrogates.

Pesticides occupy a special position among various chemical agents that are present in the environment because of to their toxicity, wide use, mainly in mixtures, and lack of action selectivity. To correlate the toxic effects to the pesticides exposure, biomarkers called endpoints are used and often use highly predictive adverse effects or death; however, there is a constant search for markers that may determine the effects of exposure before the organisms suffer from them, and these markers are the so-called surrogate endpoints. The objective of this work was to present endpoints and surrogate endpoints applied in risk assessment of occupational exposure to pesticides. After the revision of the literature, it was possible to conclude that the authors are considering different parameters as endpoint although their use is consensus as essential tools during all stages of risk assessment. The toxicological data are from traditional models however the future trend is to knowledge the effects of the exposure to several pesticides and to apply some endpoints and surrogates to monitoring the simultaneous exposure to complex mixtures.

Assessment of exposure to pesticides in rural workers in southern of Minas Gerais, Brazil.

The aim of the study was to assess of occupational exposure to pesticides in rural workers using genotoxicity test, bioindicators and clinical evaluation. Blood, urine and buccal samples from persons, rural workers exposed to a complex mixture of pesticides with organophosphates (n=94) and without organophosphates (n=94) were collected to compare the activities of cholinesterases, the levels of urinary dialkyl phosphates, genotoxicity data, from a cytome assay. Biomarkers were analysed by traditional/published methods Control group consisted of 50 other persons, non- occupationally exposed to pesticides from the city of Alfenas, Minas Gerais, Brazil. All subjects underwent a clinical evaluation. In the group exposed to organophosphates, the activity of acetylcholinesterase, butyrylcholinesterase and total cholinesterase was lower by 63.8%, 12.8%, and 14.8%, respectively, and 92.6% of the group had dialkyl phosphates present in their urine. The cytome assay was used to measure biomarkers of DNA damage (micronuclei and/or elimination of nuclear material by budding), cytokinetic defects (binucleated cells), and proliferative potential (basal cell) and/or cell death (condensed chromatin, karyorrhectic, pyknotic, and karyolytic cells). The group exposed to organophosphates showed significant changes in all these parameters compared to the control group and showed significant changes in budding, condensed chromatin and karyolytic cells compared with the group non-exposed to organophosphates. Data from the clinical evaluation showed significant changes in the central nervous, respiratory and auditory systems. The studied biomarkers are able to distinguish occupational and environmental exposure to pesticides and the data showed hazardous exposure to organophosphates and afforded valuable data to estimate the risk to cancer development.

Diazepam influences urinary bioindicator of occupational toluene exposure.

In the present study, we investigated the influence of diazepam (DZP) on the excretion of TOL by examining their urinary metabolites, hippuric acid (HA) and ortho-cresol (o-C). Male Wistar rats were exposed to TOL (20ppm) in a nose-only exposure chamber (6h/day, 5days/week for 6 weeks) with simultaneous administration of DZP (10mg/kg/day). Urinary o-C levels were determined by GC-MS, while HA, creatinine (CR), DZP and its metabolite, nordiazepam, were analysed by HPLC-DAD. The results of a Mann-Whitney U test showed that DZP influenced the urinary excretion of o-C (p<0.05). This pioneering study revealed that there was an interaction between DZP and TOL, probably by the inhibition of the CYP isoforms (CYP2B6, CYP2C8, CYP2E1, and CYP1A2) involved in the oxidative metabolism of the solvent. This is relevant information to be considered in the biomonitoring of occupational toluene exposure.

UPLC-MS/MS method for simultaneous determination of cyclophosphamide, docetaxel, doxorubicin and 5-fluorouracil in surface samples.

INTRODUCTION: There is certainly a great benefit to treatment with antineoplastic drugs for cancer patients with a life-threatening disease. However, for the workers who are exposed to these agents as part of their work practice, precautions should be taken to eliminate or reduce exposure as much as possible. OBJECTIVE: The aim of this study is to develop and validate a wipe sampling procedure followed by liquid chromatographic separation with electrospray ionization and a tandem mass spectrometric detection method for the simultaneous determination of cyclophosphamide (CP), docetaxel (DOC), doxorubicin (DOXO) and 5-fluorouracil (5-FU). METHOD: The chromatographic separation was carried out in 15min by applying a gradient elution of 0.1% formic acid and acetonitrile. MS/MS was performed on a triple quadrupole instrument in the multiple reaction monitoring (MRM) mode. RESULTS: The analytical range was linear between 3.5 to 300ng/mL for CP, 4 to 300ng/mL for DOC and DOXO and 2 to 300ng/mL for 5-FU. The present method offers a high sensitivity, with detection limits of 1.0ng/mL for CP, DOXO and DOC and 0.5ng/mL for 5-FU. The selectivity, accuracy (relative standard error between 82.3 and 113.9%) and precision (relative standard deviation between 1.2 and 14.2%) make the method suitable for the routine determination of these drugs to estimate the occupational exposure of personnel handling. CONCLUSIONS: The developed method allows a reliable assessment of exposure, which is one of the steps for evaluation the risk inherent to workers in contact with antineoplastic drugs.

Determination of parabens in serum by liquid chromatography-tandem mass spectrometry: Correlation with lipstick use.

Parabens are the most widely used preservative and are considered to be relatively safe compounds. However, studies have demonstrated that they may have estrogenic activity, and there is ongoing debate regarding the safety and potential cancer risk of using products containing these compounds. In the present work, liquid chromatography-tandem mass spectrometry was applied to determine methylparaben and propylparaben concentrations in serum, and the results were correlated with lipstick application. Samples were analyzed using liquid-liquid extraction, followed by liquid chromatography-tandem mass spectrometry. The validation results demonstrated the linearity of the method over a range of 1-20 ng/mL, in addition to the method's precision and accuracy. A statistically significant difference was demonstrated between serum parabens in women who used lipstick containing these substances compared with those not using this cosmetic (p = 0.0005 and 0.0016, respectively), and a strong association was observed between serum parabens and lipstick use (Spearman correlation = 0.7202).

On-line restricted access molecularly imprinted solid phase extraction of ivermectin in meat samples followed by HPLC-UV analysis.

A new restricted access molecularly imprinted polymer coated with bovine serum albumin (RAMIP-BSA) was synthesized, characterized and used for direct analysis of ivermectin from bovine meat samples, in a two-dimensional liquid chromatography system with UV detection. Ivermectin, 4-vynilpiridine and ethylene glycol dimethacrylate were employed as template, functional monomer and cross-linker, respectively. A BSA layer was cross-linked around the polymer, resulting in a biocompatible chemical barrier able to eliminate about 100% of protein from the samples. Ivermectin was extracted from the minced meat samples through a solvent extraction using methanol:water (70:30, v:v), and the extracts were directly injected into the two-dimensional liquid chromatography system, without any other treatment. Samples, fortified with ivermectin from 50 to 500 µg kg(-1), were used to build the analytical calibration curve (r=0.996). The limit of quantification was 50 µg kg(-1). Precision and accuracy presented variation coefficients, as well as relative errors lower than 17.0% and within -18.5% and 22.0%, respectively.