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Mistretta V.,Service de Toxicologie Clinique | Kurth W.,Service de Chirurgie de lAppareil Locomoteur | Charlier C.,Service de Toxicologie Clinique
Medecine/Sciences | Year: 2016

The placement of a hip prosthesis is one of the most common orthopedic surgical procedures. Some implants contain metal and are therefore capable of releasing metal particles like cobalt in patients who wear metal prostheses. Cobalt can be responsible of local toxicity (including metallosis, hypersensitivity reaction, and benign tumor) or systemic toxicity (including cardiomyopathy, polycythemia, hypothyroidism, and neurological disorders). To monitor potential toxicity of metal hip prostheses, an annual monitoring of patients implanted is recommended and includes clinical examination, radiological examination and blood cobalt determination. The cobalt concentration in blood allows to estimate the risk of toxicity and to evaluate the performance of the implant. The currently recommended threshold value is equal to 7 μg of cobalt per liter of blood. Our study, conducted on 251 patients over a period of 4 years, has shown that the cobalt concentration average was 2.51 μg/l in blood, with 51 patients having a cobaltemia higher than the threshold of 7 μg/l. © 2016 médecine/sciences - Inserm.


Dubois N.,Service de Toxicologie Clinique | Counerotte S.,University of Liège | Goffin E.,University of Liège | Pirotte B.,University of Liège | And 2 more authors.
Annales de Biologie Clinique | Year: 2014

The identification of a product absorbed by an opiate consumer is sometimes problematic since there is no specific biomarker for all molecules. We developed an ultra-high pressure liquid chromatography coupled to tandem mass spectrometry technique which allows the identification and the quantification of 25 opiates in plasma. The sample preparation consists in a solid-phase extraction on Oasis® MCX cartridges (Waters). The method has been validated according to FDA criteria completely for 21 substances and with some reservations for the remaining 4 analytes. This method has been applied to 80 patients treated at the University Hospital of Liege for whom the screening of opiates was positive. The identification of the product consumed was effective in 86% of cases.


Dubois N.,Service de Toxicologie Clinique | Debrus B.,University of Liège | Hubert Ph.,University of Liège | Charlier C.,Service de Toxicologie Clinique | Charlier C.,University of Liège
Acta Clinica Belgica | Year: 2010

Simultaneous determination of cocaine, opiates and amphetamines in serum by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) allowed to replace favourably gas chromatography coupled to mass spectrometry (GC-MS) used until now in our laboratory. It had to answer to accreditation demand according to Belgian Accreditation (Belac). Twenty-one deutereted internal standards were added to 500μL of serum. Sample pre-treatment consisted of solid-phase extraction using Oasis MCX cartridges 1mL, 30mg (Waters, Zellik, Belgium). Chromatographic separation was done on an Acquity HSS T3 column (2.1 x 100mm, 1.8μm, Waters). Mobile phase consisted of pH 3 ammonium formate buffer and of methanol adjusted to pH 3 with formic acid. Compounds were next analysed by tandem mass spectrometry operated in the multiple reaction monitoring (MRM) mode. The method was validated using total error approach. Twenty-seven drugs were separated in 19 minutes. The linearity of the method was acceptable in the validated range of concentrations. The bias and the relative standard deviations for repeatability and intermediate precision were acceptable. Lower and upper β-expectation tolerance limits did not exceed the acceptance limits of 20% for concentrations upper than 20μg/L and 50% for concentrations lower than 20μg/L. The limits of quantitation were lower than 7μg/L for all compounds.


Biological monitoring, also called biomonitoring, is a process to prevent and assess health risk for individuals exposed to chemical products present in environment or through workplace exposure. Biomonitoring is most often a monitoring of exposure or of effect. The exposure monitoring is currently the most widespread in toxicology. It involves the determination in biological fluids of different biomarkers, most of which are biomarkers of internal dose. These biological indicators are typically measured in blood and urine, but other biological samples can be analyzed. They are used to assess the penetration of environmental pollutants into the body. Assay results are interpreted in relation to reference values which are adapted either to occupationally exposed populations, or to general population. This interpretation and the choice of appropriate biomarker of exposure are not always obvious. Biomonitoring has some limitations despite its many advantages. It is complementary to another health prevention approach: the monitoring of ambient air. To illustrate in practice the biomonitoring of exposure, several examples of toxics and their associated biomarkers are reviewed: benzene, toluene, styrene, polycyclic aromatic hydrocarbons, chloroform, 2-hexanone and hydrogen cyanide.


Dewalque L.,Service de Toxicologie Clinique | Charlier C.,Service de Toxicologie Clinique | Charlier C.,University of Liège
Revue Medicale de Liege | Year: 2012

Endocrine disruptors are chemicals substances interfering with the hormonal system. These pollutants, present in environment, can lead to diseases in human being. In this article, we take an interest to some endocrine disrupting substances linked to decrease in sperm quality and testicular dysgenesis syndrome, two pathologies involve in masculine fertility decline. The role of environment in complex diseases as male hypofertility is questioned.


Dubois N.,Service de Toxicologie Clinique | Paccou A.P.,Waters NV SA | De Backer B.G.,Service de Toxicologie Clinique | Charlier C.J.,Service de Toxicologie Clinique | Charlier C.J.,University of Liège
Journal of Analytical Toxicology | Year: 2012

In Belgium, driving under the influence (DUI) of cannabis is prohibited and has severe legal consequences for the driver if the blood plasma concentration of Δ9-tetrahydrocannabinol (THC) exceeds 1μmg/L. A method to quantify low concentrations of THC and its hydroxylated (THC-OH) and carboxylated (THC-COOH) metabolites in plasma was developed for DUI but also for other applications. Ultrahigh-performance liquid chromatography coupled to mass spectrometry seems to be a very convenient method to combine fast chromatographic separation and good sensitivity. The method was validated according to total error approach. Chromatographic separation was achieved in a 3-min total run time. The limits of quantitation were lower or equal to 1μmg/L for all compounds. The linearity of the method was acceptable in the validated range of concentrations (from 0.5 to 50μmg/L for THC, from 0.9 to 50 μg/L for THC-OH and from 1.1 to 100μmg/L for THC-COOH). The biases were lower than 13%, and the relative standard deviations for repeatability and intermediate precision did not exceed 15%. Lower and upper β-expectation tolerance limits did not exceed the acceptance limits of 20% for concentrations higher than 2μmg/L for THC and THC-OH and higher than 4μmg/L for THC-COOH. The acceptance limits were 30% for THC and THC-OH concentrations lower than 2μmg/L and for THC-COOH concentrations lower than 4μmg/L. © The Author [2012]. Published by Oxford University Press. All rights reserved.


Dubois N.,Service de Toxicologie Clinique | Elbaz A.,French Institute of Health and Medical Research | Charlier C.,Service de Toxicologie Clinique
Acta Clinica Belgica | Year: 2010

The pathogenic role of exposure to organochlorine pesticides residues is a matter of controversy. Some of them were recently suspected to be associated with neurodegenerative diseases (Parkinson, Alzheimer, ...), especially α-hexachlorocyclohexane (α-HCH), β-HCH, γ-HCH, p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), o,p'-DDE, dieldrin, p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and o,p'-DDT. Since these organochlorine products are prohibited in Europe and USA, the blood concentrations found in general population are usually lower than 1μg/L for each compound. To allow quantification of very low concentrations, the analytical method needs to be as sensitive as possible. A gas chromatography coupled to tandem mass spectrometry method has been developed for the simultaneous determination of the eight residues, and has been validated in order to check its suitability with our objectives. Sample preparation included a double liquid-liquid extraction of the serum with a mixture of petroleum ether and diethyl ether followed by a solid phase extraction on Bond Elut LRC-Certify cartridges (130mg, Varian). Extracted sample was injected onto the gas chromatography analyzer (Agilent, 7890A). The chromatographic separation was done on a HP-5MS column (30m x 0.25mm, 0.25μm, Agilent) and compounds were then analyzed in the tandem mass spectrometer (Agilent, Triple Quad, 7000A). Two transitions were studied by molecule. The method was validated using total error approach. The linearity of the method was acceptable in the validated range of concentrations for the eight pesticides. The bias was lower than 10%, the relative standard deviations are lower than 10% for repeatability (n=3) and than 15% for intermediate precision (k=3). Lower and upper β-expectation tolerance limits did not exceed the acceptance limits of 20%. The limit of quantitation was about 0.5μg/L for all compounds.The gas chromatography coupled to tandem mass spectrometry (GC-MSMS) technology was fully convenient for the detection and the quantitative determination of 8 organochlorine residues in serum. The method had been applied to the identification and quantification of the products in blood samples obtained from patients suffering from neurodegenerative disorders.


Mistretta V.,Service de Toxicologie Clinique | Charlier C.,Service de Toxicologie Clinique
Toxicologie Analytique et Clinique | Year: 2015

Objective. Patients with metal on metal hip prosthesis (MHP) have a blood cobalt concentration higher than that of the general population. In these patients, the determination of cobalt allows to appreciate the possible toxicity of the implant and it is also a good indicator for need of revision and replacement of MHP. For this purpose, an assay method was validated and applied to patients with MHP. Method. The determination of cobalt in blood is performed on 500 1/4l of whole blood diluted 10 times in an acidic aqueous solution and after addition of 100 1/4l of a titrated solution of internal standard (500 1/4g/l of germanium). The sample is then analyzed by an inductively coupled plasma mass spectrometry (ICP-MS). The described method was validated by the total error method approach by using an analytical validation software (e-noval, Arlenda®). Results. The analytical method was validated successfully. The linearity is acceptable between 0.5 and 50 1/4g/l. The bias and imprecision values for intra- and inter-assays were lower than 5% and 8%, respectively. The uncertainty assessment is lower than 17%. The average cobalt concentration measured over a period of 1 year from 107 blood samples obtained from patients with MHP is estimated to 2.61 1/4g/l (number of patients: 98; average age: 60 years; sex-ratio: 38 men/60 women). This result is lower than the recommended threshold for this population, which is set at 7 1/4g/l of cobalt in blood. Conclusion. The described method is adequate for the determination of cobalt in blood, particularly among patients with PHM. This determination is recommended for monitoring of these patients, in combination with clinical and radiological examination. © 2015 Société Française de Toxicologie Analytique.


PubMed | Service de chirurgie de lappareil locomoteur and Service de toxicologie clinique
Type: Journal Article | Journal: Medecine sciences : M/S | Year: 2016

The placement of a hip prosthesis is one of the most common orthopedic surgical procedures. Some implants contain metal and are therefore capable of releasing metal particles like cobalt in patients who wear metal prostheses. Cobalt can be responsible of local toxicity (including metallosis, hypersensitivity reaction, and benign tumor) or systemic toxicity (including cardiomyopathy, polycythemia, hypothyroidism, and neurological disorders). To monitor potential toxicity of metal hip prostheses, an annual monitoring of patients implanted is recommended and includes clinical examination, radiological examination and blood cobalt determination. The cobalt concentration in blood allows to estimate the risk of toxicity and to evaluate the performance of the implant. The currently recommended threshold value is equal to 7g of cobalt per liter of blood. Our study, conducted on 251 patients over a period of 4 years, has shown that the cobalt concentration average was 2.51g/l in blood, with 51 patients having a cobaltemia higher than the threshold of 7g/l.


PubMed | Service de toxicologie clinique
Type: Journal Article | Journal: Annales de biologie clinique | Year: 2013

Biological monitoring, also called biomonitoring, is a process to prevent and assess health risk for individuals exposed to chemical products present in environment or through workplace exposure. Biomonitoring is most often a monitoring of exposure or of effect. The exposure monitoring is currently the most widespread in toxicology. It involves the determination in biological fluids of different biomarkers, most of which are biomarkers of internal dose. These biological indicators are typically measured in blood and urine, but other biological samples can be analyzed. They are used to assess the penetration of environmental pollutants into the body. Assay results are interpreted in relation to reference values which are adapted either to occupationally exposed populations, or to general population. This interpretation and the choice of appropriate biomarker of exposure are not always obvious. Biomonitoring has some limitations despite its many advantages. It is complementary to another health prevention approach: the monitoring of ambient air. To illustrate in practice the biomonitoring of exposure, several examples of toxics and their associated biomarkers are reviewed: benzene, toluene, styrene, polycyclic aromatic hydrocarbons, chloroform, 2-hexanone and hydrogen cyanide.

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