[show abstract][hide abstract] ABSTRACT: A rapid, sensitive and highly specific HPLC-MS/MS method with direct on-line preparation was applied for the determination of 20 common pharmaceuticals in hospital and urban wastewater. Median drug concentrations were quite similar in the majority of samples, cerca 1 μg L(-1) ranging from 0.06 to 2.67 μg L(-1) in both water. Pharmaceutical hospital contribution, below 1 %, was negligible, as compared to the huge amount in the municipal plant flow. Due to only partial elimination in the plant, hundreds of kilograms of harmful waste per year are discharged in the River Seine. Therefore, to reduce potential human and environmental exposure, a topic of major concern, an efficient drug treatment procedure should be used at the municipal plant stage in order to reduce urban wastewater pollution. The HPLC-MS/MS method could be a very useful tool to optimize the pharmaceutical wastewater treatment process.
Bulletin of Environmental Contamination and Toxicology 06/2013; · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: In 2003, we simultaneously quantified 27 metals by inductively coupled plasma-mass spectrometry (ICP-MS) in the whole blood, plasma and urine of 100 healthy volunteers. We again determined the metallic profile in whole blood and plasma during 2012. ICP-MS validated multielementary method was performed for metals in whole blood and plasma. Whole blood vanadium and chromium were quantified using ICP-MS collision cell technology. The aims of the study were to compare and assess any changes in this profile, particularly due to the environment. Healthy male/female staff volunteers (n = 106) with no professional exposure to metals, or medication containing lithium, strontium; or food supplements with trace elements and vitamins and with no metal prosthesis were included. Tobacco consumption and the number of dental amalgams were recorded. Our results demonstrated a blood lead level that had drastically decreased, i.e. reduced by half, during this period (12.5 versus 26.3 µg/L, P < 0.0001). Known differences were observed between males and females for copper and zinc; cadmium and lead were higher in smokers. Median plasmatic mercury, a specific test for dental amalgam exposure, did not significantly increase (0.38 versus 0.28 µg/L, P = 0.11). The ICP-MS metallic profile is a very practical concept that is useful for clinical, forensic and environmental toxicology, including industrial hygiene monitoring.
Journal of analytical toxicology 06/2013; · 2.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Thirty-four metals were analyzed by ICP-MS. Among these elements, anthropogenic silver, gadolinium and platinum, were representative markers of medical activities in hospital and urban wastewater. On working days, median hospital wastewater concentrations for anthropogenic silver, gadolinium, and platinum were approximately three, 13 and 27 times higher respectively than the Municipal wastewater. A drastic reduction of their emission was observed during non-working days (minus 94 % for gadolinium and 87 % for platinum). A large percentage of these metals are not trapped in the Treatment Plant, i.e. 88 % for gadolinium and 69 % for platinum. More than 4 kg and 350 g for gadolinium and platinum are respectively discharged per year in the River Seine. Therefore, it is imperative to eliminate these elements in the Plant.
Bulletin of Environmental Contamination and Toxicology 09/2012; · 1.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Due to the non-polar nature and the absence of an ionizable group on the cannabinoids, the ionization efficiency in electrospray is low and leads to poor limits of detection (LOD). The reaction of chloride dabsyl with the phenolic OH group of cannabinoids results in a product containing a tertiary amine, which is easily protonated in positive electrospray mode and can significantly improve the cannabinoids LOD. A rapid, selective and sensitive LC/MS-MS method was developed for quantitative determination of Δ(9)-tetrahydrocannabinol (THC), 11-hydroxy-Δ(9)-tetrahydrocannabinol (11-OH-THC), 11-nor-9-carboxy-Δ(9)-tetrahydrocannabinol (THC-COOH), cannabinol (CBN) and cannabidiol (CBD), in micro volume blood samples following dabsyl derivatization to enhance signal intensity. The method comprised protein precipitation followed by derivatization with dabsyl chloride and subsequent analysis using liquid chromatography-tandem mass spectrometry (LC/MS-MS). Chromatographic separation was achieved using a 150mm×2.1mm C18 analytical column maintained at 65°C and eluted with a gradient of water and acetonitrile, both containing 0.2% formic acid. The run time was 8min. The assay was successfully validated using the approach based on the accuracy profile. Lower limits of quantification (LOQ) were 0.25ng/mL for THC and THC-COOH, 0.30ng/mL for 11-OH-THC, 0.40ng/mL for CBN and 0.80ng/mL for CBD. A comparative study of cannabinoids in blood and plasma, as determined by the developed LC/MS-MS method or the in-house GC/MS-MS technique, demonstrated an excellent correlation between the two methods. Dabsylation was also tested on-line with a spiral of peek tubing placed in the LC/MS-MS column heater at 65°C before the analytical column. The results obtained with on-line dabsyl derivatization were similar to those observed off-line.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 08/2012; 905:85-95. · 2.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: In France, workplace testing of drugs of abuse and psychotropic drugs is rarely performed; meanwhile it is a major public health problem. Furthermore, France is the European country that has been associated with the highest increase of the use of drugs of abuse, particularly cannabis. So workplace biological screening of drugs of abuse and of psychotropic drugs exposure is of major concern. New analytical techniques have been developed during the last years. The authors will consider analytical screening of drugs of abuse and particularly the comparison of analytical techniques applied to urine and saliva. The advantages and the disadvantages of these two matrices will be considered. Urinary and blood quantification will be reviewed, but also the interest of hair testing to explore chronic exposure. The research of psychotropic drugs in biological fluids is also a part of this paper. New analytical trends are promising and complete analysis of these substances will bee soon routinely possible in blood using a single spot test.
[show abstract][hide abstract] ABSTRACT: In France, workplace testing of drugs of abuse and psychotropic drugs is rarely performed; meanwhile it is a major public health problem. Furthermore, France is the European country that has been associated with the highest increase of the use of drugs of abuse, particularly cannabis. So workplace biological screening of drugs of abuse and of psychotropic drugs exposure is of major concern. New analytical techniques have been developed during the last years. The authors will consider analytical screening of drugs of abuse and particularly the comparison of analytical techniques applied to urine and saliva. The advantages and the disadvantages of these two matrices will be considered. Urinary and blood quantification will be reviewed, but also the interest of hair testing to explore chronic exposure. The research of psychotropic drugs in biological fluids is also a part of this paper. New analytical trends are promising and complete analysis of these substances will be soon routinely possible in blood using a single spot test.
[show abstract][hide abstract] ABSTRACT: A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs.
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 02/2012; 885-886:1-7. · 2.78 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (Cr(VI)), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically Cr(VI) reactive intermediates and reactive oxygen species. After Cr(VI) has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of Cr(VI) to Cr(III) reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of Cr(VI) is cleared in urine as Cr(III). We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30 g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7 days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49 days. During this period Cr decreased respectively from 2088 μg/L to 5 μg/L, 631 μg/L to 129 μg/L and 3512 μg/g to 10 μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2 months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells.
Forensic science international 10/2011; 217(1-3):e8-12. · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: High dosage buprenorphine (Subutex(®)) has been prescribed as a replacement therapy for major opioid dependencies in France since 1996. However, several studies have underlined its lethal risk, especially when administered intravenously, or when combined with benzodiazepines, alcohol or other central nervous system depressants. We report three fatal buprenorphine-related poisonings after snorting, among outside protocol individuals, observed at the Forensic Medicine Unit of Caen University Hospital. Medico-legal autopsies and complementary examinations were performed. The results are presented and discussed. Lethal poisoning after snorting buprenorphine was considered the most probable cause of death. These observations illustrate the risk of fatal poisoning by buprenorphine per-nasal route, which has rarely been reported in the literature although snorting is particularly prized by individuals outside the substitution therapy. We also observed the combination of buprenorphine and alcohol. By evaluating the pharmacological characteristics of this substance, as well as the data previously published in the literature, we have attempted to explain the pathophysiological mechanisms of this particular mode of poisoning that can easily be fatal.
Forensic science international 01/2011; 204(1-3):e8-11. · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: An original liquid chromatography-tandem mass spectrometry (LC-MS-MS) method coupled to online extraction has been developed for cyanide determination in blood. A method involving fluorimetric detection after naphthalene-2,3-dicarboxyaldehyde (NDA) complexation by taurine in the presence of cyanide was previously described. Its performance was limited because of the absence of an internal standard (IS). Using cyanide isotope (13)C(15)N as IS allowed quantification in MS-MS. After the addition of (13)C(15)N, 25 μL of blood were diluted in water and deproteinized with methanol. Following derivatization with NDA and taurine for 10 min at 4°C, 100 μL was injected into the online LC-MS-MS system. An Oasis HLB was used as an extraction column, and a C18 Atlantis was the analytical column. The chromatographic cycle was performed with an ammonium formate (20 mM, pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 6 min. Detection was performed in negative electrospray ionization mode (ESI(-)) with a Quattro Micro. For quantification, transitions of derivatives formed with CN and (13)C(15)N were monitored, respectively, as follows: 299.3/191.3 and 301.3/193.3. The procedure was fully validated, linear from 26 to 2600 ng/mL with limit of detection of 10 ng/mL. This method, using a small blood sample, is not only simple, but also time saving. The specificity and sensitivity of LC-MS-MS coupled to online extraction and using (13)C(15)N as the IS make this method very suitable for cyanide determination in blood and could be useful in forensic toxicology.
Journal of analytical toxicology 01/2011; 35(3):143-7. · 2.11 Impact Factor
[show abstract][hide abstract] ABSTRACT: Drug-facilitated crime (DFC) is well known to the public, yet general practitioners and other physicians are unfamiliar with this issue, largely because toxicology is not part of the medical curriculum. This often leads to diagnostic errors. The frequency of DFC is underestimated, often owing to late examination and analytical problems. On 24 December 2002 the French authorities issued a circular defining DFC as "the administration of a psychoactive drug without the victim's knowledge, as a means of aggression"; and listing places where victims can be managed On 19 July 2005, the French Agency for Health Product Safety (Afssaps) sent a letter to all professionals potentially concerned by this issue, offering guidelines for both medical personnel and laboratory staff conducting toxicological investigations. One difficulty in drug identification is that the doses administered are often low. Toxicology laboratories need sophisticated equipment and expertise to ensure that the perpetrator is prosecuted or, alternatively, to rule out DFC. More information is needed, not only for the public but also for physicians and toxicologists. Benzodiazepines and related compounds are identified in about 75% of DFC cases.
Bulletin de l'Académie nationale de médecine 02/2010; 194(2):415-28; discussion 428-30. · 0.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Over the past decade great progress has been made in metals and metalloids analysis. This analysis is a basic stage in toxicity assessment and is indispensable in achieving a realistic evaluation of substance toxicity. A recently introduced technique, inductively coupled plasma mass spectrometry (ICP-MS) is progressively replacing atomic absorption. This analysis permits multi-elementary determinations, approximately 30 elements, with an optimal gain in sensitivity in many biological matrices: i.e. whole blood, plasma, urine, hair, nail, biopsy samples. Moreover, this method allows semiquantitative determination with an additional 30 supplementary elements, which enables the toxicologist to sufficiently estimate the toxic levels and metal exposure. The authors demonstrate that the ICP-MS could be very useful for a wide range of clinical applications. Furthermore, this procedure offers new exploration possibilities in various fields such as clinical toxicology, forensic toxicology as well as work place testing or environmental exposure and permits epidemiologic studies. This analytical method in fact also provides a new scientific approach. To our knowledge we are the first to propose: the metallic profile.
La Revue de Médecine Interne. 02/2010; 31(2):128–134.
[show abstract][hide abstract] ABSTRACT: Objectif : La surveillance biologique et la recherche d’une exposition à des métaux ou à des métalloïdes font habituellement appel à leur dosage dans le sang et les urines. Cependant, en médecine légale, ces milieux ne sont pas toujours disponibles, il est de ce fait nécessaire d’utiliser d’autres prélèvements. Si les cheveux et les ongles sont des biomarqueurs permettant de mettre en évidence une exposition au long cours, ils peuvent être le siège d’une contamination externe. Aussi, il nous a semblé intéressant d’étudier la distribution des métaux dans les tissus. Méthode : À l’occasion d’une autopsie, nous avons réalisé le dosage de 34 éléments dans les principaux tissus : Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, La, Gd, W, Pt, Hg, Tl, Pb, Bi, U, chez 21 sujets des deux sexes âgés de 19 à 57 ans. Les dosages ont été réalisés par plasma à couplage inductif équipé d’un détecteur de masse sur des échantillons congelés de divers organes : cerveau, cœur, rein, foie, poumon et muscle. Cinq cents milligrammes de tissus sont minéralisés à 70 °C avec de l’acide nitrique pur. Le minéralisat est dilué avant analyse (acide nitrique, butanol et triton) en présence d’étalons internes (indium et rhodium). Du foie de bœuf d’origine chinoise dont les concentrations de métaux sont certifiées et des cheveux provenant de l’Institut national desanté publique du Canada comportant de nombreuses valeurs de référence ont été analysés. Les résultats obtenus dans les biopsies de foie et de peau dans un cas de fibrose systémique néphrogénique (FNS) sont présentés. Résultats : La linéarité est excellente dans une large gamme de concentrations avec une pente supérieure à 0,999 pour tous les éléments. Les limites de détection sont comprises entre 8 μg/g (U) et 30 ng/g (B). La fidélité intermédiaire et la reproductibilité sont respectivement inférieures à 5 % et 10 %. Tous les éléments présentent une distribution log-normale. La répartition de nombreux métaux est homogène dans les différents organes (B, U, Ni). Des concentrations élevées de Cd sont constatées dans le rein alors qu’elles sont beaucoup plus faibles dans les autres tissus. Les organes à fonction métabolique contiennent les teneurs les plus importantes de quelques éléments (Mn, Mo). Pour l’Al, les concentrations les plus fortes sont retrouvées dans le poumon, organe en contact avec le milieu extérieur. Ces résultats sont comparés aux rares données de la littérature. Le premier cas rapporté de NSF montre une teneur hépatique en Gd 20 000 fois plus élevée que celles obtenues chez des sujets décédés. En toxicologie judiciaire, le dosage des métaux et des métalloïdes dans les tissus est d’un intérêt majeur dans un certain nombre de circonstances pour documenter le décès : liquides biologiques non disponibles, soins de conservation. Conclusion : Le dosage multi-élémentaire dans les tissus par ICP-MS constitue un marqueur d’exposition aux métaux ou aux métalloïdes très utile avec de nombreuses applications cliniques et médico-légales, à la recherche d’une exposition professionnelle, environnementale, domestique, médicale ou criminelle. Objective: Metal and metalloid determination in blood and urine is the most common application of biological monitoring for screening and diagnosis of these elements exposure. Hair and nail are of interest as a cumulative biomarker of long term exposure but they may be affected by exogenous contamination. Moreover, in some forensic cases, when blood and urine are not available it would be extremely useful to document metal distribution in deep tissues. Method: To obtain the usual values of 34 elements in the normal human body, the amounts of Li, Be, B, Al, V, Cr, Mn, Co, Ni, Cu, Zn, Ga, Ge, As, Se, Rb, Sr, Mo, Pd, Ag, Cd, Sn, Sb, Te, Ba, La, Gd, W, Pt, Hg, Tl, Pb, Bi, U, were determined in 21 female and male human cadavers, whose ages ranged from 19 to 57 years. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for frozen autopsied human organs samples (brain, heart, kidney, liver, lung, and muscle). Five hundred milligrams of tissues were digested at 70 °C with pure nitric acid and diluted (nitric acid, butanol, and triton) before analysis. Indium and rhodium were used as internal standards. Chinese bovine liver certified material and hair reference material from the Canadian Institut national de santé publique were employed to ensure optimal quality of the analysis. As an application of this multi-elementary tissue determination, the results obtained from a liver biopsy are presented in a case of gadolinium nephrogenic systemic fibrosis (Gd-NSF). Results: Linearity was excellent within a wide range with a slope higher than 0.999 for all the elements. Detection limits ranged from 8 pg/g for uranium to 30 ng/g for boron. The intra-assay and the inter-assay inaccuracies, measured as the variation coefficient were below 5% and 10% respectively. All elements showed log-normal distribution. Distribution of numerous metals in the human body was almost as uniform as B, V, Ni. Very large quantities of Cd were found in the kidney. Metabolic organs contained the highest level of some elements as Mn, Mo. Concentration of Al was greatest in the lung, tissue exposed to the exterior. These results are discussed and compared to the limited literature data. As an application, in the first French Gd-NSF case we reported, the liver Gd content was 20000 times higher than the normal concentration. For forensic toxicology, metal and metalloid tissue analyses are also of major interest in many circumstances to document death: body fluids not available, embalmed body. Conclusion: Tissue ICP-MS multi-elementary determination is a very useful metal or metalloid biomarker with various forensic and clinical applications: criminal, occupational, environmental, domestic or medical exposure to these elements.