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1.
Hum Exp Toxicol ; 43: 9603271241276981, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39226487

RESUMEN

Currently, the incidence of diquat (DQ) poisoning is increasing, and quickly predicting the prognosis of poisoned patients is crucial for clinical treatment. In this study, a total of 84 DQ poisoning patients were included, with 38 surviving and 46 deceased. The plasma DQ concentration of DQ poisoned patients, determined by liquid chromatography-mass spectrometry (LC-MS) were collected and analyzed with their complete blood count (CBC) indicators. Based on DQ concentration and CBC dataset, the random forest of diagnostic and prognostic models were established. The results showed that the initial DQ plasma concentration was highly correlated with patient prognosis. There was data redundancy in the CBC dataset, continuous measurement of CBC tests could improve the model's predictive accuracy. After feature selection, the predictive accuracy of the CBC dataset significantly increased to 0.81 ± 0.17, with the most important features being white blood cells and neutrophils. The constructed CBC random forest prediction model achieved a high predictive accuracy of 0.95 ± 0.06 when diagnosing DQ poisoning. In conclusion, both DQ concentration and CBC dataset can be used to predict the prognosis of DQ treatment. In the absence of DQ concentration, the random forest model using CBC data can effectively diagnose DQ poisoning and patient's prognosis.


Asunto(s)
Algoritmos , Diquat , Humanos , Diquat/sangre , Diquat/envenenamiento , Femenino , Masculino , Pronóstico , Adulto , Recuento de Células Sanguíneas , Persona de Mediana Edad , Herbicidas/envenenamiento , Herbicidas/sangre , Adulto Joven , Adolescente , Bosques Aleatorios
2.
Clin Toxicol (Phila) ; 62(8): 483-496, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39073455

RESUMEN

INTRODUCTION: Common major co-formulants in glyphosate-based herbicides, polyethoxylated tallow amine surfactants, are suspected of being more toxic than glyphosate, contributing to the toxicity in humans. However, limited information exists on using polyethoxylated tallow amine concentrations to predict clinical outcomes. We investigated if plasma concentrations of glyphosate, its metabolite and polyethoxylated tallow amines can predict acute kidney injury and case fatality in glyphosate poisoning. METHODS: We enrolled 151 patients with acute glyphosate poisoning between 2010 and 2013. Plasma concentrations of glyphosate, its metabolite, aminomethylphosphonic acid, and polyethoxylated tallow amines were determined in 2020 using liquid chromatography-tandem mass spectrometry. Associations between exposure and poisoning severity were assessed. RESULTS: Plasma concentrations of glyphosate and aminomethylphosphonic acid demonstrated good and moderate performances in predicting acute kidney injury (≥2), with an area under the receiver operating characteristic curve of 0.83 (95% CI 0.69-0.97) and 0.76 (95% CI 0.59-0.94), respectively. Polyethoxylated tallow amines were detected in one-fifth of symptomatic patients, including one of four fatalities and those with unsaturated tallow moieties being good indicators of acute kidney injury (area under the receiver operating characteristic curve ≥0.7). As the number of repeating ethoxylate units in tallow moieties decreased, the odds of acute kidney injury increased. Glyphosate and aminomethylphosphonic acid concentrations were excellent predictors of case fatality (area under the receiver operating characteristic curve >0.9). DISCUSSION: The 2.7% case fatality rate with 49% acute, albeit mild, acute kidney injury following glyphosate poisoning is consistent with previously published data. A population approach using model-based metrics might better explore the relationship of exposure to severity of poisoning. CONCLUSIONS: Plasma concentrations of glyphosate and its metabolite predicted the severity of clinical toxicity in glyphosate poisoning. The co-formulated polyethoxylated tallow amine surfactants were even more strongly predictive of acute kidney injury but were only detected in a minority of patients.


Asunto(s)
Lesión Renal Aguda , Glicina , Glifosato , Herbicidas , Tensoactivos , Humanos , Glicina/análogos & derivados , Glicina/envenenamiento , Glicina/sangre , Masculino , Femenino , Herbicidas/envenenamiento , Herbicidas/sangre , Persona de Mediana Edad , Tensoactivos/envenenamiento , Adulto , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/sangre , Anciano , Aminas/sangre , Aminas/envenenamiento , Organofosfonatos/sangre , Espectrometría de Masas en Tándem , Isoxazoles , Tetrazoles
3.
Front Public Health ; 12: 1333450, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38894984

RESUMEN

Objectives: Diquat poisoning is an important public health and social security agency. This study aimed to develop a prognostic model and evaluate the prognostic value of plasma diquat concentration in patients with acute oral diquat poisoning, focusing on how its impact changes over time after poisoning. Methods: This was a retrospective cohort study using electronic healthcare reports from the Second Hospital of Hebei Medical University. The study sample included 80 patients with acute oral Diquat poisoning who were admitted to the hospital between January 2019 and May 2022. Time-to-event analyses were performed to assess the risk of all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The prognostic value of plasma DQ concentration on admission was assessed by computing the area under a time-dependent receiver operating characteristic curve (ROC). Results: Among the 80 patients, 29 (36.25%) patients died, and 51 (63.75%) patients survived in the hospital. Non-survivors had a median survival time (IQR) of 1.3(1.0) days and the longest survival time of 4.5 days after DQ poisoning. Compared with non-survivors, survivors had significantly lower amounts of ingestion, plasma DQ concentration on admission, lungs injury within 24 h after admission, liver injury within 24 h after admission, kidney injury within 24 h after admission, and CNS injury within 36 h after admission, higher APACHE II score and PSS within 24 h after admission (all p < 0.05). Plasma Diquat concentration at admission (HR = Exp (0.032-0.059 × ln (t))) and PSS within 24 h after admission (HR: 4.470, 95%CI: 1.604 ~ 12.452, p = 0.004) were independent prognostic factors in the time-dependent Cox regression model. Conclusion: Plasma DQ concentration at admission and PSS within 24 h after admission are independent prognostic factors for the in-hospital case fatality rate in patients with acute oral DQ poisoning. The prognostic value of plasma DQ concentration decreased with time.


Asunto(s)
Diquat , Humanos , Estudios Retrospectivos , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Adulto , Diquat/sangre , Herbicidas/sangre , Herbicidas/envenenamiento , China
4.
J Chromatogr A ; 1722: 464846, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38579612

RESUMEN

In forensic science, glyphosate (GLYP) and glufosinate (GLUF), a class of non-selective broad-spectrum herbicides, have been frequently encountered in many fatal poisoning and suicide cases due to their widespread availability. Therefore, it is essential to develop an effective method for detecting these compounds. Some conventional methods, such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS), have been reported to detect these compounds. However, these methods are not ideal for their time-consuming and non-sensitive feature. Herein, probe electrospray ionization (PESI) tandem mass spectrometry (MS/MS), a fast and sensitive technique, was applied for the determination of GLYP and GLUF in human blood, which can obtain analytical results within 0.5 min without derivatization and chromatographic separation. After protein precipitation of blood samples, the supernatant was mixed with isopropanol and ultra-pure water (1:1 v/v). Then, 8 µL of the mixture was introduced into the plastic sample plate for PESI-MS/MS analysis. The limits of detection (LODs) of the method were 0.50 µg/mL and 0.25 µg/mL for two analytes, and the limits of quantitation (LOQs) were both 1.00 µg/mL, which are higher than the concentration of reported poisoning and fatal cases. In the linear range of 1-500 µg/mL, the regression coefficients (r2) for GLYP and GLUF were over 0.99. The matrix effects ranged from 94.8 % to 119.5 %, and the biases were below 4.3 %. The recoveries ranged between 84.8 % and 107.4 %, and the biases were below 7.6 %. Meanwhile, the method was effectively utilized to detect and quantify the blood, urine, and other samples. Consequently, the results suggest that PESI-MS/MS is a straightforward, fast, and sensitive method for detecting GLUF and GLYP in forensics. In the future, PESI-MS/MS will become an indispensable technique for polar substances in grassroots units of public security where rapid detection is essential.


Asunto(s)
Aminobutiratos , Glicina , Glifosato , Herbicidas , Límite de Detección , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem , Humanos , Glicina/análogos & derivados , Glicina/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Aminobutiratos/sangre , Espectrometría de Masas en Tándem/métodos , Herbicidas/sangre , Herbicidas/envenenamiento , Reproducibilidad de los Resultados
5.
Food Chem ; 449: 139215, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38581791

RESUMEN

Misuse of amide herbicides in the fisheries environment can pose unpredictable harm to aquatic products and ultimately human health. Thus, the development of a real-time, rapid on-site detection method is crucial. This study proposes for the first time, a paper-based visual detection method for amide herbicides in fish serum, by coating the molecularly imprinted polymer layer onto quantum dots, prepared fluorescent sensing materials (QDs@MIPs) for the detection of amide herbicides in aquatic products. These materials specifically cause fluorescence quenching in the presence of amide herbicides resulting in a color change. For practical application, this research designed a rapid test strip based on QDs@MIPs, meanwhile, incorporate a smartphone or a fluorescence spectrophotometer for qualitative and quantitative measurements, the limit of detection ranges of 0.061-0.500 µM. The method can be used for on-site evaluation of aquatic products, providing new technology for monitoring the safety of aquatic products.


Asunto(s)
Amidas , Peces , Herbicidas , Puntos Cuánticos , Herbicidas/análisis , Herbicidas/sangre , Animales , Puntos Cuánticos/química , Amidas/química , Contaminación de Alimentos/análisis , Límite de Detección , Impresión Molecular , Espectrometría de Fluorescencia/métodos
6.
Anal Bioanal Chem ; 416(12): 3073-3083, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38514583

RESUMEN

Diquat (DQ), paraquat (PQ), glufosinate (GLU), and glyphosate (GLYP) are commonly used herbicides that have been confirmed to be toxic to humans. Rapid and accurate measurements of these toxicants in clinical practice are beneficial for the correct diagnosis and timely treatment of herbicide-poisoned patients. The present study aimed to establish an efficient, convenient, and reliable method to achieve the simultaneous quantification of DQ, PQ, GLU, and GLYP in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without using derivatization or ion-pairing reagents. DQ, PQ, GLU, and GLYP were extracted by the rapid protein precipitation and liquid-liquid extraction method and then separated and detected by LC-MS/MS. Subsequently, linearity, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, extraction recovery, matrix effect, dilution integrity, and stability were evaluated to validate the method based on the FDA criteria. Finally, the validated method was applied to real plasma samples collected from 166 Chinese patients with herbicide poisoning. The results showed satisfactory linearity with low LOD (1 ng/mL for DQ and PQ, 5 ng/mL for GLU, and 10 ng/mL for GLYP, respectively) and low LOQ (5 ng/mL for DQ and PQ, 25 ng/mL for GLU and GLYP, respectively). In addition, the precision, accuracy, extraction recovery, and stability of the method were acceptable. The matrix effect was not observed in the analyzed samples. Moreover, the developed method was successfully applied to determine the target compounds in real plasma samples. These data provided reliable evidence for the application of this LC-MS/MS method for clinical poisoning detection.


Asunto(s)
Aminobutiratos , Diquat , Glicina , Glifosato , Herbicidas , Límite de Detección , Paraquat , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Glicina/análogos & derivados , Glicina/sangre , Aminobutiratos/sangre , Diquat/sangre , Diquat/envenenamiento , Paraquat/sangre , Paraquat/envenenamiento , Herbicidas/sangre , Herbicidas/envenenamiento , Cromatografía Liquida/métodos , Reproducibilidad de los Resultados
7.
Forensic Sci Int ; 327: 110910, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34425306

RESUMEN

A sensitive and rapid method for the simultaneous determination of twenty herbicides (aclonifen, lactofen, terbutryn, butylate, carbetamide, fluazifop-P-butyl, propanil, prometryn, isoproturon, terbumeton, pretilachlor, pendimethalin, cycloxydim, tri-allate, metolachlor, diuron, alloxydim, prosulfuron, triflusulfuron-methyl, and acetochlor) in human blood is reported herein. Liquid-liquid extraction coupled with ultra-pressure liquid chromatography-tandem mass spectrometry was employed for the simultaneous analysis of all compounds in 15 min. Validation parameters were studied through the estimation of the limits of detection and quantification, calibration curves, sensitivity, spiked recovery and precision. The limits of detection ranged from 0.1 to 1.0 ng/mL. The limits of quantification ranged from 0.5 to 2.0 ng/mL. Good linearity was obtained for all compounds with R2> 0.99 in all cases. Furthermore, interday precision (< 15%) and intraday precision (< 15%) were shown to be satisfactory. Recoveries in spiked blood samples were evaluated, and acceptable values (88.0%~108.8%) were found. Finally, this method was successfully applied to the determination of fluazifop-P-butyl, isoproturon and acetochlor in blood samples from real forensic cases. These results suggest that this method is reliable for rapid forensic and clinical diagnosis.


Asunto(s)
Análisis Químico de la Sangre , Herbicidas/sangre , China/epidemiología , Cromatografía Líquida de Alta Presión , Humanos , Límite de Detección , Extracción Líquido-Líquido , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Espectrometría de Masas en Tándem
8.
Toxicol Appl Pharmacol ; 417: 115463, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33631232

RESUMEN

By extending our Paraquat (PQ) work to include primates we have implemented a modelling and simulation strategy that has enabled PQ pharmacokinetic data to be integrated into a single physiologically based pharmacokinetic (PBPK) model that enables more confident extrapolation to humans. Because available data suggested there might be differences in PQ kinetics between primates and non-primates, a radiolabelled study was conducted to characterize pharmacokinetics and excretion in Cynomolgus monkeys. Following single intravenous doses of 0.01 or 0.1 mg paraquat dichloride/kg bw, plasma PQ concentration-time profiles were dose-proportional. Excretion up to 48 h (predominantly urinary) was 82.9%, with ca. 10% remaining unexcreted. In vitro blood binding was similar across Cynomolgus monkeys, humans and rat. Our PBPK model for the rat, mouse and dog, employing a single set of PQ-specific parameters, was scaled to Cynomolgus monkeys and well represented the measured plasma concentration-time profiles over 14 days. Addition of a cartilage compartment to the model better captured the percent remaining in the monkeys at 48 h, whilst having negligible effect on model predictions for the other species. The PBPK model performed well for all four species, demonstrating there is little difference in PQ kinetics between non-primates and primates enabling a more confident extrapolation to humans. Scaling of the PBPK model to humans, with addition of a human-specific dermal submodel based on in vitro human dermal absorption data, provides a valuable tool that could be employed in defining internal dosimetry to complement human health risk assessments.


Asunto(s)
Herbicidas/farmacocinética , Modelos Biológicos , Paraquat/farmacocinética , Animales , Simulación por Computador , Herbicidas/administración & dosificación , Herbicidas/sangre , Herbicidas/toxicidad , Humanos , Infusiones Intravenosas , Eliminación Intestinal , Macaca fascicularis , Paraquat/administración & dosificación , Paraquat/sangre , Paraquat/toxicidad , Ratas , Eliminación Renal , Medición de Riesgo , Absorción Cutánea , Especificidad de la Especie , Distribución Tisular , Toxicocinética
9.
Toxicol Appl Pharmacol ; 417: 115462, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33631233

RESUMEN

Paraquat dichloride (PQ) is a non-selective herbicide which has been the subject of numerous toxicology studies over more than 50 years. This paper describes the development of a physiologically-based pharmacokinetic (PBPK) model of PQ kinetics for the rat, mouse and dog, firstly to aid the interpretation of studies in which no kinetic measurements were made, and secondly to enable the future extension of the model to humans. Existing pharmacokinetic data were used to develop a model for the rat and mouse. Simulations with this preliminary model were then used to identify key data gaps and to design a new blood binding study to reduce uncertainty in critical aspects of the model. The new data provided evidence to support the model structure, and its predictive performance was then assessed against dog and rat datasets not used in model development. The PQ-specific model parameters are the same for all three species, with only the physiological parameters varying between species. This consistency across species provides a strong basis for extrapolation to other species, as demonstrated here for the dog. The model enables a wide range of PQ data to be linked together to provide a broad understanding of PQ pharmacokinetics in rodents and the dog, showing that the key aspects of PQ kinetics in these species are understood and adequately encapsulated within the model.


Asunto(s)
Herbicidas/farmacocinética , Modelos Biológicos , Paraquat/farmacocinética , Animales , Simulación por Computador , Perros , Herbicidas/sangre , Herbicidas/toxicidad , Eliminación Intestinal , Ratones , Paraquat/sangre , Paraquat/toxicidad , Unión Proteica , Ratas , Eliminación Renal , Medición de Riesgo , Especificidad de la Especie , Distribución Tisular , Toxicocinética
10.
J Clin Lab Anal ; 35(3): e23669, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33296104

RESUMEN

BACKGROUND: Paraquat and diquat are widely used in agricultural production in many countries, which are very toxic to human beings. Paraquat can be detected in some diquat solution sold in the market. The blood concentration of paraquat or diquat is an important indicator for clinical diagnosis of paraquat or diquat poisoning. So, it is very meaningful to develop a method for simultaneous determination of paraquat and diquat in human plasma. OBJECTIVE: To develop and validate a HPLC-DAD method for simultaneous determination of paraquat and diquat in human plasma and to apply it in the acute poisoning patients by these two herbicides. METHODS: Paraquat and diquat were simultaneously determined by HPLC-DAD. The plasma was treated using Waters OASIS® Column and then separated on a Thermo Hypersil GOLD (250 × 4.6 mm, 5 µm) Column with the mobile phase consisted of 75 mmol/L sodium heptane sulfonate (containing 0.1 mol/L phosphoric acid, pH 3.0) and acetonitrile (87:13, v:v) at a flow rate of 1.0 mL/min. The full-wavelength scanning was 200-400 nm, and the detection wavelength of paraquat and diquat was 257nm and 310nm, respectively. 120 and 30 plasma samples from patients with paraquat and diquat poisoning were collected and analyzed by the established method. RESULTS: The standard curve for paraquat and diquat ranged from 0.05 to 20 µg/mL, and the precision of LLOQ for paraquat was 16.49%, which was required to be less than 20%. The precision of other concentrations was less than 14.14%. The recovery of paraquat and diquat was 95.38%-103.97% and 94.79%-98.40%, respectively. The results showed that paraquat and diquat were stable under various storage conditions. 120 plasma samples of paraquat poisoning patients and 30 plasma samples of diquat poisoning patients were determined by the established method. The blood concentration of paraquat ranged from 0.10 to 20.62 µg/mL, with an average of 3.61 µg/mL, while for diquat, the concentration ranged from 0 to 26.59 µg/mL, with an average of 2.00 µg/mL. Among the diquat suspected poisoning samples, 5 samples were detected not only diquat but also paraquat, and 2 samples were detected only paraquat, no diquat. CONCLUSION: The HPLC-DAD method established in this study was high throughput, high sensitivity, simple operation, and wide linear ranges. It can be used for the screening analysis and quantitative detection of paraquat and diquat in acute poisoning patients, which can provide basis for the treatment and prognosis of these two herbicides poisoning patients.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Diquat/sangre , Paraquat/sangre , Intoxicación/sangre , Calibración , Cromatografía Líquida de Alta Presión/instrumentación , Diquat/envenenamiento , Herbicidas/sangre , Herbicidas/envenenamiento , Humanos , Límite de Detección , Paraquat/envenenamiento , Reproducibilidad de los Resultados
11.
Se Pu ; 38(11): 1294-1301, 2020 Nov 08.
Artículo en Chino | MEDLINE | ID: mdl-34213100

RESUMEN

Paraquat (PQ) and diquat (DQ) are widely used as non-selective contact herbicides. Several cases involving accidents, suicide, and homicide by PQ or DQ poisoning have been reported. Poising by PQ, which is mainly concentrated in the lungs, causes acute respiratory distress syndrome and leads to multiple organ toxicity. The toxic effects of DQ are similar to those of PQ but relatively less intense. The mortality rates in PQ and DQ poisoning are high. Simultaneous monitoring of the PQ and DQ concentrations in plasma and urine can provide valuable information for early clinical diagnosis and prognosis. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) is the main analytical method used to detect PQ and DQ in plasma and urine. As both these compounds are highly polar and water soluble, they cannot be retained effectively on a reversed-phase column with conventional mobile phases. The separation of PQ and DQ by ion-pair chromatography or hydrophilic chromatography has been reported. The use of an ion-pairing reagent helps in improving the retention capabilities of PQ and DQ. However, the sensitivity of MS detection is noticeably decreased because of ion suppression caused by the ion-pairing reagent in the mobile phase; furthermore, ion-pairing reagents may contaminate the MS system. The separation of PQ and DQ by hydrophilic chromatography is easily affected by matrix components in the sample, and their retention times are not stable. Considering PQ and DQ are bicharged cation species in solution, they are more suitable for separation by cation-exchange chromatography. A method based on ion chromatography-triple quadrupole mass spectrometry was established for the determination of PQ and DQ in plasma and urine. The plasma and urine samples were diluted with water, and then purified on a solid-phase extraction column containing a polymer-reversed phase and weak ion-exchange mixed-mode adsorbent (Oasis WCX). PQ and DQ were separated on an IonPac CS 18 analytical column (250 mm×2.0 mm, 6.0 µm) with gradient elution using a methylsulfonic acid solution electrolytically generated from an on-line eluent generation cartridge. An in-line suppressor was used to remove methylsulfonate and other anions from the eluent before the eluent entered the mass spectrometer. Between the suppressor and the ion source in MS, the addition of 3% (v/v) formic acid in acetonitrile as an organic modifier (using an auxiliary pump and a T-piece) aided desolvation in the ion source, resulted in a one-or two-fold improvement of the response, and eliminated the residual effects of the adsorption of PQ and DQ caused by ion source. The analytes were detected by triple quadrupole tandem mass spectrometry using positive electrospray ionization in the multiple reaction monitoring (MRM) mode. PQ-d8 and DQ-d4 were used as internal standards. The calibration curves for PQ and DQ showed good linear relationships in the ranges of 1.0-150 µg/L and 0.5-75 µg/L, respectively, and the correlation coefficients were > 0.999. The average matrix effects of PQ and DQ in plasma were 84.2%-89.3% and 84.7%-91.1%, while the average matrix effects of PQ and DQ in urine were 50.3%-58.4% and 51.9%-59.4%. The average recoveries of PQ and DQ in plasma were 93.5%-117% and 91.7%-112%, respectively, with relative standard deviations (RSDs) of 3.4-16.7% and 2.8%-13.2%, and that in urine were 90.0%-118% and 99.2%-116%, with relative standard deviations of 5.6%-14.9% and 2.4%-17.3% (n=6). The limits of detection of PQ and DQ in plasma and urine were 0.3 µg/L and 0.2 µg/L, respectively, with the corresponding limits of quantification being 1.0 µg/L and 0.5 µg/L. This method is sensitive and accurate, and it can be used to determine PQ and DQ for clinical diagnosis and prognosis in patients.


Asunto(s)
Diquat , Herbicidas , Paraquat , Cromatografía Líquida de Alta Presión , Diquat/sangre , Diquat/envenenamiento , Diquat/orina , Herbicidas/sangre , Herbicidas/envenenamiento , Herbicidas/orina , Humanos , Paraquat/sangre , Paraquat/envenenamiento , Paraquat/orina , Espectrometría de Masas en Tándem
12.
J Pharmacol Toxicol Methods ; 100: 106610, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31302166

RESUMEN

INTRODUCTION: Paraquat (PQ) is one of the most toxic herbicides to humans. However, it is still in use in many countries, including Japan, and many incidents, such as homicides, intentional ingestions, and occupational accidents, have been reported thus far. In PQ poisoning cases, it is possible to predict severity and prognosis using nomograms. Therefore, if the serum PQ level is determined immediately, a treatment plan can be rapidly established. However, most known analytical methods are time-consuming and therefore hardly ever contribute to patient treatment. METHODS: We developed a new method for PQ quantitation in serum by combining a probe electrospray ionization technique with mass spectrometry. This method requires virtually no serum pretreatment and can yield quantitation values in 18 s. RESULTS: We applied the proposed method to samples from real poisoning cases and compared the results with those obtained via liquid-chromatography-tandem mass spectrometry, revealing the absence of any significant differences at the 5% significance level (t(8) = 1.000, p > .05). The limits of detection and quantitation were 0.004 and 0.015 µg/L, respectively, and the calibration curve exhibited good linearity over the concentration range of 0.015-4.0 µg/mL (r2 = 0.998). DISCUSSION: As the proposed method is fast and easy to perform, it should be useful in emergency medical settings.


Asunto(s)
Herbicidas/sangre , Paraquat/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida , Herbicidas/envenenamiento , Humanos , Límite de Detección , Paraquat/envenenamiento , Factores de Tiempo
13.
J Pharm Biomed Anal ; 174: 175-181, 2019 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-31170631

RESUMEN

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.


Asunto(s)
Aminobutiratos/sangre , Glicina/análogos & derivados , Herbicidas/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Aminobutiratos/envenenamiento , Calibración , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Glicina/sangre , Glicina/envenenamiento , Herbicidas/envenenamiento , Humanos , Límite de Detección , Estándares de Referencia , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Glifosato
14.
Am J Emerg Med ; 37(8): 1600.e5-1600.e6, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31053371

RESUMEN

INTRODUCTION: This report describes changes in blood and urine concentrations of glyphosate potassium over time and their correlations with clinical symptoms in a patient with acute glyphosate potassium poisoning. CASE REPORT: A 67-year-old man visited the emergency center after ingesting 250 mL of a glyphosate potassium-based herbicide 5 h before. He was alert but presented with nausea, vomiting, and bradyarrhythmia with atrial fibrillation (tall T waves). Laboratory findings revealed a serum potassium level of 6.52 mEq/L. After treatment with an injection of calcium gluconate, insulin with glucose, bicarbonate, and an enema with polystyrene sulfonate, the patient's serum potassium level normalized and the bradyarrhythmia converted to a normal sinus rhythm. During admission, the blood and urine concentration of glyphosate and urine aminomethylphosphonic acid (AMPA, a glyphosate metabolite) was measured at regular time intervals. The patient's glyphosate blood concentration on admission was 11.48 mg/L, and it had decreased rapidly by 16 h and maintained about 1mgl/L by 70 h after admission. Urine glyphosate and AMPA levels had also decreased rapidly by 6 h after admission. DISCUSSION: Glyphosate potassium poisoning causes hyperkalemia. Blood concentrations of glyphosate were decreased rapidly by 16 h after admission, and urine concentrations were also decreased by 6 h after admission.


Asunto(s)
Glicina/análogos & derivados , Herbicidas/sangre , Herbicidas/envenenamiento , Hiperpotasemia/inducido químicamente , Anciano , Arritmias Cardíacas/inducido químicamente , Glicina/sangre , Glicina/envenenamiento , Glicina/orina , Herbicidas/orina , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/tratamiento farmacológico , Masculino , Náusea/inducido químicamente , Potasio/sangre , Intento de Suicidio , Resultado del Tratamiento , Vómitos/inducido químicamente , Glifosato
15.
Clin Exp Nephrol ; 23(4): 474-483, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30859350

RESUMEN

BACKGROUND: The herbicide paraquat (1, 1'-dimethyl-4, 4'-bipyridylium dichloride; PQ) is a poison well-known to cause delayed mortality due to acute kidney injuries (AKI). This study examines the changes in serum amino acids (AAs) metabolite profiles as surrogate markers of renal cell metabolism and function after paraquat poisoning. METHODS: To identify the metabolic profiling of free serum AAs and its metabolites, serum from 40 paraquat-poisoned patients with or without AKI is collected. LC-MS/GC-MS is performed to analyze AA molecules. A Cox proportional hazard model was used to assess for incidence of AKI. Receiver operating characteristic (ROC) curve is applied to evaluate AKI occurrence and prognosis. RESULTS: A total of 102 serum AAs and its metabolites were identified. Compared with non-AKI patients, 37 varied significantly in AKI patients. The univariate Cox proportional hazard model analysis revealed that the estimated PQ amount, plasma PQ concentration, urine PQ concentration, APACHE, SOFA scores and 16 amino acids correlated with the incidence of AKI. Further analyses revealed that 3-methylglutarylcarnitine, 1-methylimidazoleacetate, and urea showed higher cumulative hazard ratios for the occurrence of AKI during follow-up (P < 0.05). The area under the curve (AUC) of 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were 0.917, 0.857, 0.872, respectively. CONCLUSION: 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were associated with AKI in patients with paraquat intoxication.


Asunto(s)
Lesión Renal Aguda/sangre , Aminoácidos/sangre , Carnitina/análogos & derivados , Glutaratos/sangre , Herbicidas/envenenamiento , Imidazoles/sangre , Paraquat/envenenamiento , Urea/sangre , Lesión Renal Aguda/inducido químicamente , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Carnitina/sangre , Estudios de Casos y Controles , Femenino , Herbicidas/sangre , Herbicidas/orina , Humanos , Masculino , Metaboloma , Persona de Mediana Edad , Paraquat/sangre , Paraquat/orina , Intoxicación/sangre , Intoxicación/orina , Modelos de Riesgos Proporcionales , Curva ROC , Adulto Joven
16.
Carbohydr Polym ; 214: 317-327, 2019 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-30926003

RESUMEN

Development of novel biocompatible sensor material suitable for modest, cost-effective, and rapid practical application is a demanding research interest in the field of electroanalytical chemistry. In this context, for the first time, we utilized biocompatible chitosan-pectin biopolyelectrolyte (CS-PC BPE) complex for the simultaneous electroreduction of an important antibiotic drug (metronidazole-MNZ) and herbicide (metribuzin-MTZ). This sensor reveals an attractive welfares such as simplicity, biocompatibility, and low production cost. Under optimized experimental conditions, the electroanalytical investigation confirmed that CS-PC BPE modified glassy carbon electrode (CS-PC BPE/GCE) was found to sense MNZ and MTZ in the nanomolar range. Moreover, as-prepared CS-PC BPE/GCE exhibited prominent selectivity, stability, and reproducibility. Additionally, the possible MNZ and MTZ sensing mechanism of CS-PC BPE/GCE have been discussed in detail. Lastly, real sample analysis was also carried out and revealed from several investigations that the CS-PC BPE/GCE is a good electrochemical sensor system for the detection of targeted analytes.


Asunto(s)
Materiales Biocompatibles/química , Quitosano/química , Metronidazol/sangre , Pectinas/química , Polielectrolitos/química , Triazinas/sangre , Antibacterianos/sangre , Antibacterianos/química , Carbono/química , Quitosano/síntesis química , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Electrodos , Tecnología Química Verde/métodos , Herbicidas/sangre , Herbicidas/química , Humanos , Límite de Detección , Metronidazol/química , Peso Molecular , Oxidación-Reducción , Pectinas/síntesis química , Reproducibilidad de los Resultados , Triazinas/química , Viscosidad
18.
Mol Cell Endocrinol ; 482: 45-56, 2019 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-30550814

RESUMEN

The aim of the present study was to compare the effect of oral and subcutaneous exposure to a glyphosate-based herbicide (GBH) on the female reproductive system, specifically in the ovaries and uterus of prepubertal lambs. To this end, ewe lambs were exposed to a s.c. (n: 5) or an oral (n: 5) environmentally relevant dose of GBH (2 mg/kg/day) or to vehicle (controls, n: 12), from postnatal day (PND) 1 to PND14. Serum glyphosate and aminomethylphosphonic acid (AMPA) concentrations were measured on PND15 and PND45. The ovaries and uterus were obtained and weighed on PND45. Ovarian follicular dynamics and uterine morphological features were determined by picrosirius-hematoxylin staining. The proliferation marker Ki67 was evaluated by immunohistochemistry in ovarian and uterine samples. Glyphosate but not AMPA was detected in serum of exposed lambs on PND15, whereas neither glyphosate nor AMPA were detected on PND45. Controls were negative for glyphosate and AMPA on PND15 and PND45. GBH exposure did not affect ovarian or uterine weight. However, on PND45, the ovary of GBH-exposed lambs showed altered follicular dynamics, increased proliferation of granulosa and theca cells, and decreased mRNA expression of FSHR and GDF9, whereas their uterus showed decreased cell proliferation but no alterations in the histomorphology or gene expression. In conclusion, GBH exposure altered the ovarian follicular dynamics and gene expression, and the proliferative activity of the ovaries and uterus of lambs. It is noteworthy that all the adverse effects found in the ovaries and uterus of both GBH-exposed groups were similar, independently of the administration route.


Asunto(s)
Glicina/análogos & derivados , Herbicidas/efectos adversos , Ovario/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Útero/efectos de los fármacos , Administración Oral , Animales , Animales Recién Nacidos , Proliferación Celular , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Glicina/efectos adversos , Glicina/sangre , Glicina/farmacología , Factor 9 de Diferenciación de Crecimiento/genética , Herbicidas/sangre , Herbicidas/farmacología , Inyecciones Subcutáneas , Isoxazoles/sangre , Tamaño de los Órganos/efectos de los fármacos , Ovario/citología , Ovario/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/genética , Receptores de HFE/genética , Oveja Doméstica , Tetrazoles/sangre , Útero/citología , Útero/metabolismo , Glifosato
19.
Wei Sheng Yan Jiu ; 47(6): 993-997, 2018 Nov.
Artículo en Chino | MEDLINE | ID: mdl-30593335

RESUMEN

OBJECTIVE: To establish a simple and rapid ultra-performance liquid chromatography tandem mass spectrometry( UPLC-MS/MS) method for the determination of paraquat in serum, and to apply to the toxicokinetics of paraquat in rats. METHODS: The samples separated on ACQUITY UPLC BEH HILIC column( 2. 1 mm × 50 mm, 1. 7 µm)with acetonitrile-50 mmol/L ammonium formate( 0. 4% formic acid) as mobile phase. The analytes were analyzed using ESI operating in the positive multiple reaction monitoring( MRM) mode. The method was used in toxicokinetic study in poisoned rat. Toxicokinetic parameters were calculated by WinNonlin 7. 0 statistical software. RESULTS: Paraquat was linear in the range of 0. 3-1000. 0 µg/L, the recovery rate was 89. 0%-107. 7%, and the relative standard deviation( RSD) 1. 9%-13. 8%( n = 6). Toxicokinetic parameterswere as follows: C_(max), T_(max)and T_(1/2) were( 46. 50 ± 5. 11) mg/L, 0. 167 h, ( 63. 2 ±16. 2) h, respectively. CONCLUSION: This method is highly sensitive, high accuracy and is suitable for the analysis of paraquat in the toxicokinetic study in rats.


Asunto(s)
Herbicidas , Paraquat , Espectrometría de Masas en Tándem , Animales , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Herbicidas/sangre , Herbicidas/toxicidad , Paraquat/sangre , Paraquat/toxicidad , Ratas , Toxicocinética
20.
Chem Res Toxicol ; 31(10): 1080-1085, 2018 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-30230318

RESUMEN

We have documented that the herbicide propanil is immunotoxic in mice, and our in vitro tissue culture experiments largely recapitulate the in vivo studies. Laboratory studies on environmental contaminants are the most meaningful when these studies are conducted using concentrations that approximate levels in the environment. Many techniques to measure the distribution and pharmacokinetics (PK) on compounds rely on techniques, such as liquid scintillation counting (LSC) of radio-labeled starting compound, that require concentrations higher than environmental levels. The aim of this study was to compare tissue PK after exposure to propanil concentrations more relevant to levels of exposure to agricultural workers and the general population to concentrations previously reported for laboratory studies. To this end, we conducted a study to measure propanil distribution in three immune organs, using ultrasensitive accelerator mass spectrometry (AMS). We used two doses: the lower dose modeled levels expected in the environment or long-term occupational exposure to low doses, while the higher dose was to model the effects of an accidental exposure. Our results showed that the distribution and PK profiles from these two different concentrations was markedly different. The profile of the high dose (concentration) exposure was indicative of saturation of the detoxifying capability of the animal. In contrast, at the lower environmentally relevant concentration, in vivo concentrations of propanil in spleen, liver, and blood dropped to a very low level by 720 min. In conclusion, these studies highlight the differences in PK of propanil at these two doses, which suggests that the toxicity of this chemical should be re-investigated to obtain better data on toxic effects at doses relevant for humans.


Asunto(s)
Herbicidas/farmacocinética , Propanil/farmacocinética , Animales , Radioisótopos de Carbono/química , Relación Dosis-Respuesta a Droga , Femenino , Semivida , Herbicidas/sangre , Herbicidas/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Propanil/sangre , Propanil/farmacología , Bazo/efectos de los fármacos , Bazo/metabolismo
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