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Crunelle C.L.,University of Antwerp | Yegles M.,University of Luxembourg | Nuijs A.L.N.V.,University of Antwerp | Covaci A.,University of Antwerp | And 10 more authors.
Drug and Alcohol Dependence | Year: 2014

Background: Ethyl glucuronide (EtG) is a minor alcohol metabolite that has been proposed as a stable marker in hair to detect and quantify alcohol consumption over long time periods. Methods: We provide an outline of currently available techniques for EtG hair sample analysis and highlight the pitfalls related to data interpretation. The literature of EtG analysis has been reviewed from January 1980 up to August 2013. In addition, we present an overview of the clinical and forensic studies which have used EtG quantification in hair as a marker for alcohol consumption/abstinence and we provide suggestions for future research. Results: EtG is a stable marker in hair that can be used to detect and quantify alcohol consumption over long time periods. This alcohol metabolite remains in hair after complete elimination of alcohol. Currently, there are three main analytical techniques used to quantify EtG in hair: gas chromatography-mass spectrometry (GC-MS), gas chromatography-tandem mass spectrometry (GC-MS/MS), and liquid chromatography-tandem mass spectrometry (LC-MS/MS). No standardized protocols are yet available for the analysis of EtG levels in hair samples, and the current protocols vary in sample preparation and extraction procedures. Variables such as hair length, cosmetic treatment, gender, and pathophysiological conditions influence the final results and should be taken into account. Conclusions: EtG quantification in hair is a useful tool for the objective detection of alcohol consumption over extended time periods, but care should be taken when interpreting the results. © 2013 Elsevier Ireland Ltd.


Zouaoui K.,Martin Luther University of Halle Wittenberg | Dulaurent S.,Martin Luther University of Halle Wittenberg | Gaulier J.M.,Martin Luther University of Halle Wittenberg | Moesch C.,Martin Luther University of Halle Wittenberg | And 2 more authors.
Forensic Science International | Year: 2013

Acute intoxications after ingesting glyphosate are observed in suicidal or accidental cases. Despite low potential toxicity of this herbicide, a number of fatalities and severe outcomes are reported. Indeed, some authors have described the clinical features associated with blood and urine concentrations following intoxication. The purpose of this study is to describe the clinical feature and determinate the utility of the glyphosate concentration in blood and urine and the dose taken for predicting clinical outcomes. In 13 glyphosate poisoning cases treated in our laboratory within 7 years period from 2002 to 2009, we registered clinical observations and collected blood and urine samples to HPLC-MS-MS analysis. We classified our patients by the intoxication severity using simple clinical criteria. We obtained clinical observations from 10 patients and the others three patients were treated in forensic cases. Among the 10 patients, one was asymptomatic, 5 had mild to moderate poisoning and 2 had severe poisoning. There were 6 deaths whose 3 were forensic cases. The most common symptoms were oropharyngeal ulceration (5/10), nausea and vomiting (3/10). The main altered biological parameters were high lactate (3/10) and acidosis (7/10). We also noted respiratory distress (3/10), cardiac arrhythmia (4/10), hyperkaleamia, impaired renal function (2/10), hepatic toxicity (1/10) and altered consciousness (3/10). In fatalities, the common symptoms were cardiovascular shock, cardiorespiratory arrest, haemodynamic disturbance, intravascular disseminated coagulation and multiple organ failure. Blood glyphosate concentrations had a mean value of 61. mg/L (range 0.6-150. mg/L) and 4146. mg/L (range 690-7480. mg/L) respectively in mild-moderate intoxication and fatal cases. In the severe intoxication case for which blood has been sampled, the blood glyphosate concentration was found at 838. mg/L. Death was most of the time associated with larger taken dose (500. mL in one patient) and high blood glyphosate concentrations. To predict clinical outcomes and to guide treatment support in patients who ingested glyphosate, blood concentrations of this compound and the taken dose have been useful. © 2013 Elsevier Ireland Ltd.


van Nuijs A.L.N.,University of Antwerp | Abdellati K.,University of Antwerp | Bervoets L.,University of Antwerp | Blust R.,University of Antwerp | And 4 more authors.
Journal of Hazardous Materials | Year: 2012

The stability of nine illicit drugs and metabolites in influent wastewater at relevant conditions (20. °C and at pH 7.5) was evaluated during 26. h (in 1. h intervals) to assess whether significant in-sewer processes of degradation or formation occur. This assessment is important for the sewage epidemiology approach, which uses concentrations of illicit drugs and metabolites in influent wastewater to back-calculate amounts of these substances used by a community or population. The results of this study showed that amphetamine, methamphetamine, ecstasy and EDDP (metabolite of methadone) are stable in wastewater for 12. h and longer. For benzoylecgonine and methadone, a modest formation in the course of time was observed (0.2% per h and 0.4% per h, respectively), while for cocaine (40% degradation after 12. h), ecgonine methylester (20% degradation after 12. h), and 6-monoacetylmorphine (20% degradation after 12. h), a clear decrease in concentrations in time was seen. These findings suggest that for compounds with a significant stability issue, it is important to take their behavior into account when performing back-calculations in sewage epidemiology. However, this study also highlights the need of future research regarding transformation pathways of the individual compounds. © 2012 Elsevier B.V..


Crunelle C.L.,University of Antwerp | Cappelle D.,University of Antwerp | Covaci A.,University of Antwerp | van Nuijs A.L.N.,University of Antwerp | And 7 more authors.
Drug and Alcohol Dependence | Year: 2014

Background: Ethyl glucuronide (EtG) is a minor alcohol metabolite that accumulates in hair and is proposed as a stable marker for the detection of chronic and excessive alcohol consumption above a cut-off level of 30. pg/mg hair. A correlation between drinking behavior and EtG hair concentrations is observed, but large variability exists. Aims: To investigate the correlation between alcohol consumption and hair EtG concentrations in alcohol dependent patients, and the effect of gender differences as a factor for the variability on this correlation. Methods: EtG was measured by gas chromatography coupled to mass spectrometry in the hairs (first 3. cm) of 36 alcohol dependent patients (25 males/11 females) starting and alcohol detoxification program. Factors that possibly influence EtG content in hair (except age and gender) were excluded. Detailed retrospective alcohol consumption was obtained over the last 3 months using the Timeline Follow Back interview. Results: Median total alcohol consumption over 3 months was 13,050. g pure alcohol (range 60-650. g/day). Hair EtG concentrations varied between 32 and 662. pg/mg. There was a statistically significant linear and positive correlation between hair EtG and amounts of alcohol consumed (Pearson r= 0.83; p<. 0.001), in both males (Pearson r= 0.83; p<. 0.001) and females (Pearson r= 0.76; p= 0.007). Conclusions: There is a linear correlation, with no significant effect of gender, between hair EtG concentrations and amounts of alcohol consumed in alcohol-dependent individuals. Analysis of EtG in hair can be applied to estimate retrospective alcohol consumption in both male and female alcohol dependent subjects using the same cut-off. © 2014 Elsevier Ireland Ltd.


Binz T.M.,Laboratoire National Of Sante | Villani N.,Laboratoire National Of Sante | Neels H.,University of Antwerp | Neels H.,Inhalation Toxicology Research Institute | Schneider S.,Laboratoire National Of Sante
Forensic Science International | Year: 2012

A sensitive and accurate LC-MS/MS method for the identification and quantification of 5 oral anti-diabetics (glipizide, glibenclamide, gliclazide, gliquidone and metformin) in serum and hair was developed using glibornuride as the internal standard. We have developed a rapid and robust extraction procedure by using acetonitrile for serum protein precipitation and methanol for the extraction of anti-diabetics from hair. Anti-diabetics (ADs) were separated by UPLC over a C18 column and detection was performed on a Waters Xevo TQ MS mass spectrometer in positive ionization mode using electrospray ionization. Each AD was identified by three specific ion transitions in multiple reaction monitoring (MRM) mode. The method was validated according to international guidelines. For all compounds the variation coefficient (CV) was <20%, and accuracies ranged from 85 to 115% in serum and hair. The limits of detection (LODs) were <1.5. ng/mL for all ADs in serum and <3.59. pg/mg in hair. Recoveries varied from 56.41% (gliclazide) to 67.58% (glipizide) in serum and from 68% (gliclazide) to 91.2% (metformin) in hair. The method was successfully applied to quantify ADs in serum of 33 patients and in hair of 15 patients. © 2012 Elsevier Ireland Ltd.


Shwetha A.,Inhalation Toxicology Research Institute | Hosetti B.B.,Inhalation Toxicology Research Institute | Dube P.N.,Inhalation Toxicology Research Institute
International Journal of Environmental Research | Year: 2012

Effect of zinc cyanide on protein and certain metabolites content and some enzymes activities was evaluated in liver, muscle and gill tissues of the freshwater fish, Cirrhinus mrigala, during exposure and following cessation of exposure. Fish exhibited significant alterations in the biochemical parameters in all tissues studied. Levels of total protein decreased in all tissues, where as free amino acids (FAA) and protease activities significantly increased (P<0.05). Similarly decrease was observed in the ammonia level with increased urea and glutamine levels at all exposure periods. The enzymes involved in the protein metabolism altered under the zinc cyanide intoxication. Increase in the protease and aminotransferases revealed amplified transamination processes. Significant increase of phosphatases indicated increased rate of phosphorylation and transport of molecules across the cell membrane. Withdrawal study also exhibited significant recovery in all above biochemical parameters, in all tissue after the 7th day post recovery treatment. Present study exhibited negative effects of zinc cyanide on protein metabolism. Fish with low protein content were not fit for human consumption. Patterns of effects on intermediary metabolism suggest avenues to determine the mechanisms by which such effects occur.


Montiel V.,Cliniques St Luc | Gougnard T.,Inhalation Toxicology Research Institute | Hantson P.,Cliniques St Luc | Hantson P.,Catholic University of Louvain
European Journal of Emergency Medicine | Year: 2011

Intravenous lipid emulsion (ILE) has been proposed as a rescue therapy for severe local anesthetic drugs toxicity, but experience is limited with other lipophilic drugs. An 18-year-old healthy woman was admitted 8 h after the voluntary ingestion of sustained-release diltiazem (3600 mg), with severe hypotension refractory to fluid therapy, calcium salts, and high-dose norepinephrine (6.66 μg/kg/min). Hyperinsulinemic euglycemia therapy was initiated and shortly after was followed by a protocol of ILE (intralipid 20%, 1.5 ml/kg as bolus, followed by 0.25 ml/kg over 1h). The main finding attributed to ILE was an apparent rapid decrease in insulin resistance, despite a prolonged serum diltiazem elimination half-life. Diltiazem is a lipophilic cardiotoxic drug, which could be sequestered in an expanded plasma lipid phase. The mechanism of action of ILE is not known, including its role in insulin resistance and myocardial metabolism in calcium-channel blocker poisoning. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Swortwood M.J.,Florida International University | Boland D.M.,Inhalation Toxicology Research Institute | Decaprio A.P.,Florida International University
Analytical and Bioanalytical Chemistry | Year: 2013

Recently, clandestine drug lab operators have attempted to bypass controlled substances laws and regulations with "designer" compounds chemically and pharmacologically similar to controlled substances. For example, "bath salts" have erupted onto the scene as "legal highs" containing cathinone analogs that have produced severe side effects in users worldwide. These products have sparked concern among law enforcement agencies, and emergency bans have been placed on the sale of such items. Despite the increasing number of designer drugs available, there are few comprehensive screening techniques for their detection and quantification in biological specimens. The liquid chromatography triple quadrupole tandem mass spectrometry (LC-QQQ-MS/MS) method presented here encompasses over thirty important compounds within the phenethylamine, tryptamine, and piperazine designer drug classes. Analytes were determined by LC-QQQ-MS/MS in the multiple-reaction monitoring mode after mixed-mode solid-phase extraction. The bioanalytical method was fully validated according to recommended international guidelines. The assay was selective for all analytes with acceptable accuracy and precision. Limits of quantification were in the range of 1-10 ng/mL for each compound with limits of detection near 10 pg/mL. In order to evaluate its applicability in a forensic toxicological setting, the validated method was used to analyze post-mortem specimens from two cases that were suspected of containing designer drugs. The method was able to identify and quantify seven of these compounds at concentrations as low as 11 ng/mL. The method should have wide applicability for rapid screening of important new drugs of abuse at high sensitivity in both post- and ante-mortem forensic analysis. © 2012 Springer-Verlag Berlin Heidelberg.


Watanabe K.P.,Inhalation Toxicology Research Institute | Saengtienchai A.,Inhalation Toxicology Research Institute | Tanaka K.D.,Inhalation Toxicology Research Institute | Ikenaka Y.,Inhalation Toxicology Research Institute | Ishizuka M.,Inhalation Toxicology Research Institute
Comparative Biochemistry and Physiology - C Toxicology and Pharmacology | Year: 2010

Scattering coumarin derivative rodenticides in broad areas have caused primary- and secondary-poisoning incidents in non-target wild birds. In this study, we compared factors determining warfarin sensitivity between bird species and rats based on vitamin K 2,3-epoxide reductase (VKOR) kinetics, VKOR inhibition by warfarin and warfarin metabolism assays. In VKOR characterization, chickens and ostriches showed significantly lower enzymatic efficiencies than rats (one-sixth and one-third, respectively), suggesting bird species depend more on a non-VKOR vitamin K source. On the other hand, the inhibition constants (K i) of VKOR for warfarin were significantly different between chickens and ostriches (11.3 ± 2.5 μM and 0.64 ± 0.39 μM, respectively). Interestingly, the ostrich K i was similar to the values for rats (0.28 ± 0.09 μM). The K i results reveal a surprising possibility that VKOR in some bird species are easily inhibited by warfarin. Warfarin metabolism assays also showed a large inter-species difference in bird species. Chickens and ostriches showed higher metabolic activity than that of rats, while mallards and owls showed only a slight ability to metabolize warfarin. In this study, we clarified the wide inter-species difference that exists among birds in xenobiotic metabolism and sensitivity to a rodenticide. © 2010 Elsevier Inc. All rights reserved.


Boogaerts T.,University of Antwerp | Covaci A.,University of Antwerp | Kinyua J.,University of Antwerp | Neels H.,University of Antwerp | And 2 more authors.
Drug and Alcohol Dependence | Year: 2016

Background: In recent years, scientific evidence has emerged that wastewater-based epidemiology can deliver complementary information concerning the use of different substances of abuse. In this study, the potential of wastewater-based epidemiology in monitoring spatial and temporal trends in alcohol consumption in different populations in Belgium has been examined. Methods: Concentrations of ethyl sulphate, a minor Phase-II metabolite of ethanol, in 163 influent wastewater samples from eight wastewater treatment plants in Belgium in the period 2013-2015 were measured with liquid chromatography coupled to tandem mass spectrometry and used to estimate alcohol consumption. Results: The highest levels of alcohol consumption were detected in the metropoles Antwerp and Brussels compared to smaller villages. Annual variations were detected, with a higher alcohol consumption measured in 2013 compared with 2014. The weekly pattern showed a clear week and weekend difference in alcohol use, with intermediate levels on Monday and Friday. The results were extrapolated and a use of 5.6 L pure alcohol per year per inhabitant aged 15+ has been estimated in Belgium. The comparison with available information on drinking habits of the Belgian population further demonstrated the usefulness of the wastewater-based epidemiology approach. Conclusions: This is the largest wastewater-based epidemiology study monitoring alcohol consumption to date, demonstrating that objective and quick information on spatio-temporal trends in alcohol consumption on a local and (inter)national scale can be obtained. © 2016 Elsevier Ireland Ltd.

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