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Biomedical subjects

P Kintz

Publications and source records attributed to P Kintz.

At least 37 records · Page 2Linked to original sources
PubMed2002

Doping control for methenolone using hair analysis by gas chromatography-tandem mass spectrometry.

A sensitive, specific and reproducible method for the quantitative determination of methenolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml 1 M NaOH, 15 min at 95 degrees C, in presence of 1 ng testosterone-d3 used as internal standard. The homogenate was neutralized and extracted using consecutively a solid-phase (Isolute C18 eluted with methanol) and a liquid-liquid (pentane) extraction. The residue was derivatized by adding 50 microl MSTFA-NH4I-2-mercaptoethanol (1000:2:5, v/v/v), then incubated for 20 ml at 60 degrees C. A 1.5-microl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl-95% methylsiloxane, 30 m x 0.25 mm I.D., 0.25 microm film thickness) of a Hewlett-Packard (Palo Alto, CA, USA) gas chromatograph (6890 Series). Methenolone was detected by its parent ion at m/z 446 and daughter ions at m/z 208 and 195 through a Finnigan TSQ 700 MS-MS system. The assay was capable of detecting 1 pg/mg of methenolone when approximately 100 mg hair material was processed. Linearity was observed for methenolone concentrations ranging from 2 to 100 pg/mg with a correlation coefficients of 0.965-0.981. Intra-day and between-day precisions at 2, 10 and 25 pg/mg were 10.9-14.1% and 13.7-16.8%, respectively, with an extraction recovery of 97.6%. The analysis of a strand of hair obtained from two bodybuilders, revealed the presence of methenolone at the concentrations of 7.3 and 8.8 pg/mg.

Anabolic Agents↗
PubMed2002

Blood investigation in a fatality involving the veterinary drug T-61.

A case involving an acute fatality resulting from self-administration of about 30 mL of T-61, a euthanasia solution, consisting of a mixture of embutramide, mebezonium, and tetracaine, in a 58-year-old veterinarian is presented. Forensic investigations consisted of an external body examination, during which 5 mL of fluorinated femoral blood was collected. Embutramide and tetracaine were quantitated using gas chromatography coupled to mass spectrometry after extraction with chloroform/isopropanol/n-heptane (50:17:33, v/v) at pH 9.5 and separation on an HP5-MS capillary column. Mebezonium was quantitated using liquid chromatography coupled to mass spectrometry after ion-pair extraction (saturated KI solution) with methylene chloride at pH 5.4 and separation on a 5-mm Nucleosil C18 column. Blood concentrations were 43.0, 6.5, and 0.21 mg/L for embutramide, mebezonium, and tetracaine, respectively. No other drugs, including ethanol, were detected.

Amides↗
PubMed2002

[Crime under the influence of psychoactive drugs: the problem of the duration of detection].

On a regular basis, the media presents the potential risks of the use of psycho-active compounds, including misused pharmaceuticals (flunitrazepam, GHB) or drugs of abuse (cannabis, LSD, ecstasy). Ethanol is also frequently encountered. These drugs can be used for recreational purposes by addicts or can be observed after sexual assaults (drugs spiked in food). Forensic toxicology can be involved in several situations to document impairment, such as: crime under influence, date rape, driving under influence, psychiatric disorders, determination of the cause of death... In some particular situations, it can be very cautious to investigate exposure to psycho-active drugs, due to late sampling of biological specimens. To enhance the window of detection of 3 specific drugs, the authors propose the following: 1. Use of an ultra-sensitive technique, such as GC/MS/MS/NCI for 7-aminoflunitrazepam; 2. Use of a cumulative specimen, such as sweat for GHB and 3. Use of a metabolite with a long half-life, such as ethyl glucuronide for ethanol.

Cause of Death↗
PubMed2002

[Use of gamma-hydroxybutyric acid (GHB) at rave parties and in date rape in France: myth of reality?].

Since many years gamma-hydroxybutyric acid (GHB) is presented as very popular in rave-parties and for bodybuilders. It seems to be a controversy between media coverage and the results of toxicological analysis done in high-level laboratories. In order to clarify this problem, we compiled the data of 6 laboratories. They used the same analytical method by GC/MS. Depending the laboratory, the limit of detection was 1-2 micrograms/mL and the limit of quantification was 2.5-5 micrograms/mL. Two labs where looking for GHB in each forensic case (100 and 150 cases a year). Others labs performed GHB analysis only on specific request (each 10 cases a year). Mean time between ingestion of GHB and blood/urine sampling was 12-48 h. Mean time between sampling and analysis was much higher (a few hours to a few month. All samples were stored at +4 degrees C. Only 3 cases were considered as positive (blood GHB: 165, 132 and 114 micrograms/mL, urine GHB: 7450 and 436 micrograms/mL) They were admitted in an hospital EU. Interpreting results remains very difficult because GHB is endogenous, present in blood and urine, and its half-life is very short. One has to report only "positive" GHB results when amounts are higher than 5 micrograms/mL in blood and 10 micrograms/mL in urine. Obviously, forensic toxicologists have to play a very important part in diagnosis of GHB intoxications and estimating its frequency. Actually, because the lack of data in France, it is not possible to answer the question asked in the title of this paper.

Forensic Medicine↗
PubMed2002

[Rapid determination of propofol in biological specimens and hair by HS-GC/MS].

This paper proposes an original method for the determination of propofol in biological specimens. For example, hair specimens are cut into small pieces and incubated overnight in Soerensen buffer at 40 degrees C. After headspace preparation of the biological specimens spiked with tetrahydrofurane (internal standard), the analytes are transferred to the gas chromatograph and separated on a HP Wax capillary column. Detection is achieved in SIM mode (propofol: m/z 117, 163 and 178) on a mass spectrometer operating in electronic impact mode. The developed procedure is easy (full-automated), rapid (no extraction- or derivatization-step), sensible and accurate. After validation of the analytical method (linearity, extraction recovery, repeatability, limit of detection), this new procedure was applied to forensic cases.

Anesthetics, Intravenous↗
PubMed2002

Hair analysis of seven bodybuilders for anabolic steroids, ephedrine, and clenbuterol.

Several bodybuilders, all winners of international competitions, were arrested for trafficking of a number of doping agents including anabolic steroids, ephedrine, beta-adrenergics, human chorionic gonadotropin, antidepressants, and diuretics. In accordance with the recent French law against doping, the judge asked to test seven bodybuilders to identify doping practices. Hair and urine specimens were collected for analysis. After decontamination, a 100 mg hair strand was pulverized in a ball mill, hydrolyzed, extracted, and derivatized to be tested by GC/MS for anabolic steroids, beta-adrenergic compounds, ephedrine, and other doping agents. Urine was analyzed for anabolic steroids and metabolites, beta-adrenergic compounds, ephedrine, and human chorionic gonadotropin, in addition to a broad spectrum screening with GC/MS. The following compounds were detected in urine: ephedrine (29 and 36 ng/mL, n = 2), clenbuterol (0.2 to 0.3 ng/mL, n = 3), norandrosterone (4.7 to 100.7 ng/mL, n = 7), norethiocholanolone (0.9 to 161.8 ng/mL, n = 6), stanozolol (1 to 25.8 ng/mL, n = 4), methenolone (2.5 to 29.7 ng/mL, n = 4), testosterone (3 to 59.6 ng/mL, n = 7), epitestosterone (1 to 20.4 ng/mL, n = 7) and ratio testosterone/epitestosterone >6 for four subjects (18.5 to 59.6). The following drugs were detected in hair: ephedrine (0.67 and 10.70 ng/mg, n = 2), salbutamol (15 to 31 pg/mg, n = 3), clenbuterol (15 to 122 pg/mg, n = 6), nandrolone (1 to 7.5 pg/mg, n = 3), stanozolol (2 to 84 pg/mg, n = 4), methenolone (17 and 34 ng/ml, n = 2), testosterone enanthate (0.6 to 18.8 ng/mg, n = 5), and testosterone cypionate (3.3 to 4.8 ng/mg, n = 2). These results document the doping practice and demonstrate repetitive exposure to anabolic compounds and confirm the value of hair analysis as a complement to urinalysis in the control of doping practice.

Adult↗
PubMed2001

Deaths involving buprenorphine: a compendium of French cases.

Buprenorphine at high dosage became available in France in 1996, as a substitution treatment for heroin addicts. Since this date, numerous deaths were attributed to this drug. This paper reports two original series of 39 and 78 fatalities involving buprenorphine observed at the Institute of Legal Medicine of Strasbourg and at 13 other French forensic centers, respectively. The files were recorded from January 1996-May 2000. The first 20 fatalities that were previously published were excluded from this epidemiological study. From these 117 subjects, 96 were male (82%). Buprenorphine and its primary metabolite norbuprenophine were assayed in post-mortem blood by HPLC/MS (n=11 labs) or by GC/MS (n=3 labs). Blood levels for buprenorphine ranged from 0.5 to 51.0ng/ml (mean 10.2ng/ml) and 0.1 to 76ng/ml (mean 12.6ng/ml) in Strasbourg and the other centers, respectively. Blood levels for norbuprenorphine ranged from 0.2 to 47.1ng/ml (mean 8.2ng/ml) and <0.1 to 65ng/ml (mean 10.6ng/ml) in Strasbourg and the other centers, respectively. The mean values appear to be within the therapeutic range. Buprenorphine was identified in 24 of the 26 hair samples assayed in Strasbourg, at concentrations ranging from 10 to 1080pg/mg. Intravenous injection of crushed tablets, a concomitant intake of psychotropics (especially benzodiazepines and neuroleptics) and the high dosage of the buprenorphine formulation available in France appear as the major risk factors for such fatalities. In addition, two suicide-related deaths were also observed, with blood buprenorphine concentrations at 144 and 3276ng/ml.

Adult↗
PubMed2001

Doping control for nandrolone using hair analysis.

A sensitive, specific and reproducible method for the quantitative determination of nandrolone in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride. The hair sample (about 100 mg) was solubilized in 1 ml NaOH IN, 15 min at 95 degrees C, in presence of 10 ng nandrolone-d(3) used as an internal standard. The homogenate was neutralized and extracted using consecutively a solid phase (Isolute C18) and a liquid--liquid (pentane) extraction. The residue was derivatized by adding 50 microl MSTFA/NH4I/2-mercaptoethanol (1000:2:5; v/v/v), then incubated for 20 min at 60 degrees C. A 4-microl aliquot of the derivatized extract was injected into the column (HP5-MS capillary column, 5% phenyl--95% methylsiloxane, 30 m x 0.25 mm i.d. x 0.25 mm film thickness) of a Hewlett Packard (Palo Alto, CA) gas chromatograph (6890 Series) via a Hewlett Packard (7673) autosampler. The assay was capable of detecting 0.5 pg of nandrolone per mg of hair when approximately 100 mg of hair were processed. Linearity was observed for nandrolone concentrations ranging from 1 to 50 pg/mg with a correlation coefficient of 0.997. Intra-day and between-day precisions at 10 pg/mg were 11.2 and 15.1%, respectively, with an extraction recovery of 81.7%. The analysis of three strands of hair, obtained from three bodybuilders, revealed the presence of nandrolone at the concentration of 1, 3.5 and 7.5 pg/mg.

Doping in Sports↗
PubMed2000

[Drug tests on 198 drivers involved in an accident].

OBJECTIVES: A prospective analytical study was performed in a large population of drivers implicated in traffic accidents to determine the significance of drug levels observed in blood, urine, saliva and sweat and which assays are best to perform in each sample. METHODS: Samples of blood (7.5 ml), urine (10-20 ml), saliva (salivette Sarstedt) and sweat (cosmetic pad spiked with water-isopropanol) were systematically collected in drivers implicated in non-fatal traffic accidents from March to November 1999. The samples were tested for pharmaceuticals (barbiturates, benzodiazepines, anti-depressants, neuroleptics, antiepileptics and antihistamines) and for drugs of abuse by hyphenated chromatographic methods (LC/DAD, GC/MS and LC/MS). RESULTS: A total of 198 drivers (bicycle, motorbike, car, truck) were tested (age range 13-57 years, 82% males). Blood alcohol was positive in 27 cases (13.7%), ranging from 0.11 to 3.19 g/l (mean 1.49 g/l), being > 0.5 g/l in 21 cases. Cannabis was the most frequently observed illicit drug (9.6% of the cases). Its formal pharmacological effect could only be documented by blood testing using GC/MS. Even in the hospital setting, urine collection was difficult. In 16% of the cases, this fluid was missing. Parent compounds were excreted in both saliva and sweat. On-site devices devoted to urine and metabolites were inapplicable. Concentrations in sweat and saliva were very low, particularly for benzodiazepines and cannabis. There was also a risk of external contamination for sweat. CONCLUSION: Saliva might be a good substitution fluid for blood for sample taking on the road side.

Accidents, Traffic↗
PubMed2000

Testing of the anabolic stanozolol in human hair by gas chromatography-negative ion chemical ionization mass spectrometry.

A sensitive, specific and reproducible method for the quantitative determination of stanozolol in human hair has been developed. The sample preparation involved a decontamination step of the hair with methylene chloride and the sonication in methanol of 100 mg of powdered hair for 2 h. After elimination of the solvent, the hair sample was solubilized in 1 ml 1 M NaOH, 15 min at 95 degrees C, in the presence of 10 ng stanozolol-d3 used as internal standard. The homogenate was neutralized and extracted using consecutively a solid-phase (Isolute C18) and a liquid-liquid (pentane) extraction. After evaporation of the final organic phase, the dry extract was derivatized using 40 microl MBHFA-TMSI (1000:20, v/v), incubated for 5 min at 80 degrees C, followed by 10 microl of MBHFBA, incubated for 30 min at 80 degrees C. The derivatized extract was analyzed by a Hewlett-Packard GC-MS system with a 5989 B Engine operating in the negative chemical ionization mode of detection. Linearity of the detector response was observed for stanozolol concentrations ranging from 5 to 200 pg/mg with a correlation coefficient of 0.998. The assay was capable of detecting 2 pg of stanozolol per mg of hair when approximately 100 mg hair material was processed, with a quantification limit set at 5 pg/mg. Intra-day precision was 5.9% at 50 pg/mg and 7.8% at 25 pg/mg with extraction recoveries of 79.8 and 75.1%, respectively. The analysis of a 3-cm long hair strand, obtained from a young bodybuilder (27 year old) assuming to be a regular user of Winstrol (stanozolol, 2 mg), revealed the presence of stanozolol at the concentration of 15 pg/mg.

Adult↗
PubMed2000

Drugs in prehistory: chemical analysis of ancient human hair.

Concern about drug abuse in modern populations has led to the development of specific methods for identification of cocaine, opiates and cannabis in human hair. Drug use in prehistory can provide indirect evidence of interpopulational contact and social stratification. This paper reports drug evaluation in nineteen ancient hair samples from archaeological sites in northern Chile. Each sample was tested for the presence of traces of cocaine, opiates and cannabis, in order to establish a standard methodology for studies of drug use among prehistoric groups. Although results are negative, this absence of evidence could be due to two main causes: (1) the individuals evaluated did not use any drugs, which does not mean that other members of their cultural group did, or (2) the wide range of known drugs studied did not consider some group specific drugs, derived from local or imported plants, thus meaning that a greater drug range must be tested. In any case, our study confirms that drug testing in prehistoric samples is viable. However, in order to determine what kind of substances were used in prehistoric times new patterns that incorporate all drugs which are not part of the western pharmacopeia must be created. Finally, a methodology for the study of drug use among prehistoric groups using ancient hair samples is described.

Cannabinoids↗
PubMed2000

Clozapine dose-concentration relationships in plasma, hair and sweat specimens of schizophrenic patients.

The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200-700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40 degrees C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in concentrations ranging from 30 to 1016 ng/ml in plasma (n = 22), from 0.17 to 34.24 ng/mg in hair (n = 23) and from 49 to 5609 ng/patch in sweat (n = 20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better dose-concentration relationship was observed in our study between daily dose and hair concentration (r = 0.542, P < 7%) or between daily dose and sweat concentration (r = 0.589, P < 6%), but with wide variations for patients at the same posology. However, the idea of using quantitative drug measurements in hair or sweat to ascertain whether a patient has taken his treatment exactly as prescribed will remain inapplicable.

Antipsychotic Agents↗
PubMed2000

Pharmacological criteria that can affect the detection of doping agents in hair.

When positive drug results are reported, a common interpretive question posed is whether or not it is possible to put a quantitative finding into context. A standard answer to this inquiry is that a positive hair testing result can be interpreted as meaning that the donor has chronically or repetitively used the drug identified in the hair, but that chronic or repetitive are not defined in the same way for all individuals. The Society of Hair Testing published on June 16, 1999, a consensus opinion on the use of hair in doping situations. However, although accepted in most courts of justice, hair analysis is not yet recognised by the International Olympic Committee. To be considered as a valid specimen for doping control, some issues still need to be addressed. The scientific community has demonstrated significant concern over the proper role that hair drug testing should serve in toxicological applications. Among the unanswered questions, five are of critical importance: (1) What is the minimal amount of drug detectable in hair after administration? (2) What is the relationship between the amount of the drug used and the concentration of the drug or its metabolites in hair? (3) What is the influence of hair color? (4) Is there any racial bias in hair testing? (5) What is the influence of cosmetic treatments? The present report documents scientific findings on these questions, with particular attention to the applications of hair in doping control.

Anabolic Agents↗
PubMed2000

Identification of ten corticosteroids in human hair by liquid chromatography-ionspray mass spectrometry.

This paper describes a screening procedure based upon high-performance liquid chromatography-ionspray mass spectrometry for the identification of ten corticosteroids in human hair: triamcinolone, prednisolone, prednisone, methylprednisolone, cortisone, cortisol, beta- and dexamethasone, flumethasone and beclomethasone. Hair strands were washed in methylene chloride, pulverized in a ball mill and 50 mg of the powdered hair were incubated in 1 ml Soerensen buffer, pH 7.6 for 16 h at 40 degrees C, in presence of 50 ng cortisol-d3 used as internal standard. Purification of the incubation medium was achieved on SPE C18 Isolute extraction columns. The eluates were evaporated to dryness and resuspended in 30 microliters MeOH before analysis by HPLC-IS-MS in positive and negative modes of detection. The validation parameters were found satisfactory for a corticosteroid screening procedure. The correlation coefficient of the calibration curve ranged from 0.939 to 0.997, showing linearity between 0.1 and 10 ng/mg, excepted for beclomethasone which was between 0.2 and 10 ng/mg. Extraction recovery at 4 ng/mg ranged from 43.2 to 85.7%. Repeatability (CV values) at 4 ng/mg ranged from 6.1 to 17.5%. The limits of detection ranged from 0.03 to 0.17 ng/mg for a signal-to-noise ratio of 2. The detection of prednisone and beclomethasone in three hair specimens obtained from forensic and clinical cases have documented corticosteroids incorporation into human hair.

Adrenal Cortex Hormones↗
PubMed2000

The hair analysis proficiency testing program of the French Society of Analytical Toxicology.

In an effort to improve laboratories performing hair analysis in forensic cases, the French Society of Analytical Toxicology (S.F.T.A.) has implemented a proficiency testing program since 1992. Actually about 10 laboratories are participating. Each survey is dedicated to one analyte or one pharmacological class: opiates (6-monoacetylmorphine, morphine and codeine), cocaine and benzoylecgonine, tetrahydrocannabinol, buprenorphine and norbuprenorphine, beta-blockers (metoprolol, atenolol), beta 2-agonists (salbutamol, clenbuterol). Animal hair was tested for clenbuterol. Prior to sending, hair samples were reduced to a powdered form, well mixed to ensure homogeneity, and then tested by GC/MS or HPLC/MS. Results confirm those obtained in a preliminary study on opiates and cocaine analysis in hair: a common analytical procedure has to be used by all the participants, including hydrolysis of hair. It is essential to work on authentic drug-positive hair samples and not on spiked samples. Participation at this program is free of charge and considered as an educational tool. Comparison of the results with those of other laboratories in Europe and USA shows that the analytical methods used during this program are in accordance with all the other procedures.

Chromatography, High Pressure Liquid↗
PubMed2000

The distribution of laudanosine in tissues after death from atracurium injection.

A case is presented involving an acute fatality resulting from self-administration of atracurium, a muscle relaxant by a 45-year-old nurse. In the body, atracurium undergoes a spontaneous non-enzymatic degradation to laudanosine and an acrylate moiety. Laudanosine was quantified using gas chromatography coupled to mass spectrometry after extraction with chloroform-isopropanol-n-heptane (50:17:33 v/v) at pH 9.5 and separation on a HP5-MS capillary column. Laudanosine was subject to postmortem redistribution due to release from drug-rich tissues such as the lung and heart. The heart blood (917 ng/ml) to peripheral blood (390 ng/ml) ratio was 2.4. No other drugs, including ethanol were detected.

Atracurium↗