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1.
Int J Legal Med ; 136(3): 695-704, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35190879

RESUMEN

After the use of thallium as rat poison was banned, the knowledge about the severe and treacherous course of poisonings with this toxic metal has widely been lost. In the present case, the male victim sustained two insidious poisoning attacks in 2017 and 2020 by the perpetrator, his female life partner. In the first poisoning episode, he suffered from increasing heavy pain of the abdomen, stinging pain of both legs, persistent obstipation, hyperesthesia, and, after about 2 weeks, tuft-wise loss of hair as typical symptoms of the thallium poisoning. Within 7 weeks, he was successively examined in six hospitals with a wide variety of diagnostic methods, but a conclusive explanation of the complaints was not found. The possibility of a metal intoxication was then suggested by the perpetrator who privately arranged the analysis of a blood sample with the result of 175 µg/l thallium. Although a criminal poisoning was assumed, the perpetrator was not identified. After the victim left the perpetrator, she subtly executed a second poisoning attack with thallium sulfate (blood level 1230 µg/l after 1 day, urine level 4760 µg/l after 10 days, and hair concentrations 3.26-0.49 from proximal to distal in 9 segments). The perpetrator was sentenced to 10.5 years imprisonment for grievous bodily harm and attempted murder. Because of the behavior of the perpetrator, a Munchausen by proxy syndrome was discussed as a motivation of the first poisoning but was excluded by the psychiatric expert because of a missing antisocial personality disorder.


Asunto(s)
Intoxicación , Talio , Animales , Femenino , Cabello , Homicidio , Humanos , Masculino , Motivación , Dolor , Ratas
2.
Int J Legal Med ; 134(2): 523-532, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31965236

RESUMEN

AIMS: Small children are expected to be abstinent from alcohol, and children's hair is frequently used as the blank matrix for calibration of the alcohol consumption marker ethyl glucuronide (EtG). The basal EtG concentrations of total abstainers were described to be 0.3-2.1 pg/mg (Pirro et al. 2013). It is examined whether this assumption is valid for children from families with addiction background. METHODS: In a social support system for families with drug and/or alcohol addicted parents, 161 hair samples from 126 children (age 1-14 years, hair segment 0-3 cm) were analyzed for EtG by a validated LC-MS/MS method (LOD 0.56 pg/mg, LLOQ 2.3 pg/mg). For comparison, ethyl palmitate (EtPa) was measured and hair samples from parents were included. EtG ≥ 3 pg/mg was considered as an alarming result for children. RESULTS AND DISCUSSION: EtG concentrations between 3.0 and 42.6 pg/mg (mean 9.55 pg/mg, median 6.40 pg/mg) were measured for 25 samples (15.5%, age 22 × 1-5 years, 3 × 9-11 years). Elevated EtPa (0.15-0.46 ng/mg) was found in 6 samples and cocaethylene (0.02-0.07 ng/mg) was detected in 5 samples with high cocaine findings. Hair results of one or both parents indicated drug abuse in 12 from 14 cases (85.7%) if both parents were tested. CONCLUSION: Although accidental or voluntary intake of alcoholic beverages cannot be excluded, the external contamination of children's hair by EtG-containing wine and sweat or urine of the alcohol abusing parents is assumed to be the most probable explanation for the positive EtG results in hair of 1-5-year-old children.


Asunto(s)
Consumo de Bebidas Alcohólicas , Glucuronatos/análisis , Cabello/química , Menores , Detección de Abuso de Sustancias , Adolescente , Conducta Adictiva , Biomarcadores/análisis , Niño , Preescolar , Cromatografía Liquida , Cocaína/análogos & derivados , Trastornos Relacionados con Cocaína , Femenino , Humanos , Lactante , Masculino , Ácidos Palmíticos , Padres , Espectrometría de Masas en Tándem
4.
Int J Legal Med ; 129(1): 69-84, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25138383

RESUMEN

Contrary to the illegal use of any form of manufactured cocaine, chewing of coca leaves and drinking of coca tea are allowed and are very common and socially integrated in several South American countries. Because of this different legal state, an analytical method for discrimination between use of coca leaves and abuse of processed cocaine preparations is required. In this study, the applicability of hair analysis for this purpose was examined. Hair samples from 26 Argentinean coca chewers and 22 German cocaine users were analysed for cocaine (COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), cuscohygrine (CUS) and hygrine (HYG) by hydrophilic interaction liquid chromatography (HILIC) in combination with triplequad mass spectrometry (MS/MS) and hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS). The following concentrations (range, median, ng/mg) were determined in hair of the coca chewers: COC 0.085-75.5, 17.0; NC 0.03-1.15, 0.12; BE 0.046-35.5, 6.1; EME 0.014-6.0, 0.66; CE 0.00-13.8, 0.38; CIN 0.005-16.8, 0.79; TRO 0.02-0.16, 0.023; CUS 0.026-26.7, 0.31. In lack of a reference substance, only qualitative data were obtained for HYG, and two metabolites of CUS were detected which were not found in hair of the cocaine users. For interpretation, the concentrations of the metabolites and of the coca alkaloids in relation to cocaine were statistically compared between coca chewers and cocaine users. By analysis of variance (ANOVA) significant differences were found for all analytes (α = 0.000 to 0.030) with the exception of TRO (α = 0.218). The ratios CUS/COC, CIN/COC and EME/COC appeared to be the most suitable criteria for discrimination between both groups with the means and medians 5-fold to 10-fold higher for coca chewers and a low overlap of the ranges between both groups. The same was qualitatively found for HYG. However, these criteria cannot exclude cocaine use in addition to coca chewing. In this regard screening for typical cutting agents can be helpful and led to the detection of levamisole (21×), lidocaine (6×) and paracetamol (3×) in the 22 samples from German cocaine users, whereas no levamisole, lidocaine (3×) and paracetamol (1×) were found in hair from the Argentinean coca chewers. These criteria have to be confirmed for South American cocaine consumers including smokers of coca paste and may be different because of different composition of the drug and other use habits.


Asunto(s)
Trastornos Relacionados con Cocaína/diagnóstico , Cabello/química , Masticación , Hojas de la Planta , , Acetaminofén/análisis , Acetona/análogos & derivados , Acetona/análisis , Adolescente , Adulto , Anciano , Cromatografía Liquida , Coca , Cocaína/análogos & derivados , Cocaína/análisis , Contaminación de Medicamentos , Control de Medicamentos y Narcóticos/legislación & jurisprudencia , Femenino , Toxicología Forense/métodos , Humanos , Levamisol/análisis , Lidocaína/análisis , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Pirrolidinas/análisis
5.
Drug Test Anal ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38686500

RESUMEN

Combined use of alcohol and illicit drugs is a serious health and social problem. In this study, it was examined, whether a relationship between alcohol and drug abuse can be ascertained by comparison of alcohol marker and drug concentrations in hair. In the frame of a social support system for families with parental abuse of illicit drugs, hair samples were analyzed between 2011 and 2022 for methadone, heroin (6-acetylmorphine), cocaine, amphetamine, ecstasy (MDMA), cannabinoids (THC), and the alcohol markers ethyl glucuronide (EtG) and ethyl palmitate (EtPa). For 1314 hair samples from adolescent and adult family members, the hair results show a prevalence of combined occasional or regular drug use and social or abusive alcohol use of 41%-60% except heroin (35%). The drug concentrations were statistically compared in the three categories of abstinence or moderate drinking, social drinking, and alcohol abuse. For the most frequently detected drug cocaine (n = 703), a significant increase of the concentrations with rising alcohol consumption was found. The frequent detection of cocaethylene proved the preferred simultaneous intake of both substances. For THC (n = 489), no significant difference between the alcohol consumer groups was seen. Concerning the less frequently detected methadone (n = 89), 6-acetylmorphine (n = 92), amphetamine (n = 123), and MDMA (n = 105), no clear trend between drug and alcohol marker results was determined. It is concluded that the evaluation of hair results is an appropriate way to study the extent of combined drug-alcohol consumption and complements other studies based on acquisition of consumption data by interview or questionnaire.

6.
Ther Drug Monit ; 35(6): 737-52, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24263638

RESUMEN

BACKGROUND: Children living in homes with drug-addicted parents are in a steady danger of poisoning and may suffer from neglect, maltreatment, and lagging behind in development. Hair analysis could be a suitable way to examine this endangering exposure to drugs. METHODS: Hair samples from 149 children (aged 1-14 years) living with parents substituted by methadone and/or suspected for abuse of illegal drugs, and from 124 of the parents in a German community were investigated by liquid chromatography-hybrid quadrupole time-of flight mass spectrometry and by headspace solid phase microextraction gas chromatography-mass spectrometry for methadone, heroin, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines and their metabolites or degradation products (32 compounds). RESULTS: From the children's hair, only in 35 samples, no drugs were detected. Cannabinoids were found in 56 samples, in 20 of them as the only drug. In the remaining 95 samples, methadone was identified 35 times with additional use of illegal drugs in 28 cases. Drug use in the children's environment was obvious for heroin in 44 cases, cocaine in 73 cases, amphetamine or ecstasy in 6 cases, and diazepam in 8 cases. The concentrations varied from limit of quantification to 2.16 ng/mg of methadone, 11.1 ng/mg of 6-acetylmorphine, 17.8 ng/mg of cocaine, 3.29 ng/mg of amphetamine, and 0.72 ng/mg of Δ-tetrahydrocannabinol. In general, hair from younger children contained higher concentrations than from their elder siblings. Systemic incorporation of methadone, cocaine, or cannabinoids appeared likely from detection of the nonhydrolytic metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine in 11 cases, norcocaine in 16 cases, and 11-nor-9-carboxy-Δ-tetrahydrocannabinol in 9 cases. Within the families, hair samples of children and parents provided often the same drug pattern. External deposition from smoke and by contact with contaminated surfaces or parent's hands and systemic deposition after passive smoking, administration, or oral intake by hand-to-mouth transfer were discussed as alternative incorporation mechanisms into hair. CONCLUSIONS: Altogether, investigation of children's hair proved to be a useful way to detect endangering drug use in their environment and lead to a more thorough inspection and measures to improve their situation in many of the cases.


Asunto(s)
Hijo de Padres Discapacitados , Cabello/química , Drogas Ilícitas/análisis , Metadona/análisis , Detección de Abuso de Sustancias/métodos , Adolescente , Niño , Preescolar , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Alemania , Humanos , Lactante , Espectrometría de Masas/métodos , Padres , Microextracción en Fase Sólida/métodos , Trastornos Relacionados con Sustancias/rehabilitación
7.
Rapid Commun Mass Spectrom ; 26(12): 1407-14, 2012 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-22592984

RESUMEN

RATIONALE: Liquid chromatography/tandem mass spectrometry (LC/MS/MS) is frequently used for analysis of cannabinoids in drug abuse control. Despite differences in structure, the isomers Δ(9) -tetrahydrocannabinol (THC) and cannabidiol (CBD) provide identical fragment spectra after positive electrospray ionization (ESI). For elucidation of the reason, hydrogen/deuterium (H/D) exchange experiments were performed. METHODS: Solutions of THC and CBD in D(2) O/acetonitrile (50:50, v/v) were flow-injected into acetonitrile as the mobile phase and measured by hybrid quadrupole-time-of-flight mass spectrometry (FI-QTOF-MS) in targeted MS/MS mode. The MS and collision-induced dissociation (CID) spectra at 10, 20 and 40 eV were interpreted with respect to number and position of exchanged hydrogen atoms. For comparison the same measurements were preformed in H(2) O, after addition of 0.5% formic acid and with negative ESI. RESULTS: Depending on injected volume and position in the response curve, up to 7 or 8 hydrogen atoms were exchanged by deuterium in THC or CBD. Positive ESI CID spectra were available for precursors with up to 4 exchanged D-atoms and showed that besides the OH groups also an H/D exchange at carbon atoms of the non-aromatic part of the molecules occurred for both THC and CBD. After negative ESI, no H/D exchange in addition to the OH groups and different CID spectra of both substances was found. CONCLUSIONS: Injection of the investigated substances in D(2) O and measurement by FI-QTOF-MS proved to be an efficient way to perform H/D exchange experiments. The results were interpreted as an acid-catalyzed in-source equilibration between THC and CBD leading to the same precursor ions and to an H/D exchange in the methyl groups under the increased acidic conditions in the positive ESI droplets. Therefore, in positive LC/ESI-MS/MS, peak identification by CID spectra or by abundance ratio of multiple reaction monitoring (MRM) transitions is not sufficient for unambiguous discrimination between THC and CBD and must be supported by retention time or other experimental evidence.


Asunto(s)
Cannabidiol/química , Medición de Intercambio de Deuterio/métodos , Dronabinol/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Acetonitrilos , Óxido de Deuterio , Formiatos , Isomerismo
8.
Int J Legal Med ; 126(5): 791-9, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22773311

RESUMEN

BACKGROUND: Despite the growing importance of ethyl glucuronide (EtG) in hair for detection of chronic excessive alcohol consumption, the mechanism of incorporation is not yet clear. Deposition from sweat is believed to be the main route. In order to get more information, EtG was determined in daily shaved beard hair after single higher alcohol doses. METHODS: Three volunteers drank within 5.5 h 153, 165 and 200 g ethanol followed by abstinence. Daily shaved beard hair was analysed for EtG using a validated liquid chromatography-tandem mass spectrometry method with a limit of quantification of 2 pg/mg. RESULTS: For all three volunteers, small concentrations of EtG were already detected 9 h after end of drinking. The concentrations increased to maxima of 182, 242 and 74 pg/mg on days 2 to 4 and then gradually decreased to limit of quantification on days 8 to 10. DISCUSSION: The time course of EtG is discussed based on literature data about anatomic dimensions of the hair root, physiology of hair growth, kinetics of EtG formation and elimination in blood, and in comparison to literature results about drugs in beard hair. It follows that for beard hair the predominant portion of EtG is incorporated in the upper part of the hair root between suprabulbar region and isthmus leading to a positive zone of about 3 mm (8-9 days) after a single drinking event. Deposition from sweat which is only possible into the residual hair stubble after shaving and in the infundibulum down to the sebaceous gland mouth was found to be of minor importance but could play a greater role in long hair. CONCLUSION: It is concluded that EtG in hair fulfils the prerequisites for time-resolved interpretation of segmental concentrations and that a single excessive drinking can be well detected in sufficiently short hair segments. However, in the routinely investigated 3-cm proximal scalp hair segment and using the cutoff of 7 pg/mg, a negative result can be expected with high probability because of dilution by negative hair.


Asunto(s)
Consumo de Bebidas Alcohólicas/legislación & jurisprudencia , Glucuronatos/análisis , Cabello/química , Adulto , Intoxicación Alcohólica/diagnóstico , Biomarcadores/análisis , Cromatografía Liquida/métodos , Relación Dosis-Respuesta a Droga , Alemania , Folículo Piloso/química , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Espectrometría de Masas en Tándem/métodos
9.
Forensic Sci Int ; 331: 111148, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34923263

RESUMEN

BACKGROUND: Hair analysis of parents and their children was regularly used since 2011 as a diagnostic tool in a social support project for families with known or suspected abuse of conventional illegal drugs and revealed a high incidence of cocaine, cannabinoids, amphetamines, ecstasy and heroin. In this context, the prevalence of new psychoactive substances (NPS) in these families should be important for a realistic estimate of the situation. METHODS: The extracts of 1537 hair samples from 318 children (age 1-14 years), 44 adolescents and 611 adults, which were collected and tested for conventional drugs between June 2016 and April 2021 and frozen at -20 °C, were reanalyzed by a validated LC-MS/MS method (limits of quantitation 5-24 pg/mg) for 33 cathinones, 10 phenylethylamines, 5 piperazines including the antidepressant trazodone, 2 tryptamines, 9 designer benzodiazepines, 4 synthetic opioids and 4 ketamine-like substances including phencyclidine. RESULTS: Between one and up to five from 42 of these substances were detected in 227 samples (14.8%). The most frequently detected substances were benzedrone (62x), α-pyrrolidinovalerophenone (41x), N-ethylamphetamine (29x), dimethyltryptamine (13x) and pyrovalerone (11x). The quantification was possible only for 34 results of 15 drugs and the remaining majority of the results were unambiguously identified below LLOQ. The relative frequency of conventional drugs in the 227 NPS positive samples was higher than in all 1310 NPS negative samples for cocaine (69.6% vs. 56.0%), heroin (6-acetylmorphine 8.8% vs. 4.9%), amphetamine (16.3% vs. 7.7%) and MDMA (16.3% vs. 7.0%) but was similar for THC (38.3% vs. 36.3%) and benzodiazepines (1.8% vs. 1.7%). The high prevalence of N-ethylamphetamine can be explained as a byproduct of the illicit amphetamine synthesis from benzaldehyde and nitroethane rather than as a separate drug or as a combined metabolite of amphetamine and ethanol. The isolated appearance of 3-trifluoromethylphenylpiperazine in 9 hair samples collected in January 2017 can be caused either by its use as an NPS or by its formation as a metabolite of the medical drug flibanserin. The results were compared within 17 families whose members were tested at the same time and showed positive NPS results. The detected drugs agreed between both parents only in about half of the cases whereas the drugs found in children's hair was always detected also in hair of one or both parents. CONCLUSION: The re-testing of hair extracts for NPS after long-time storage in frozen state enables an impression about the relative high prevalence in the tested population group, despite the limitation by partial degradation of the substances and the corresponding impossibility in quantitative assessments. In addition to conventional drugs, the hair test for these substances should be useful in unclear cases of child's welfare endangerment and in family law.


Asunto(s)
Cocaína , Drogas Ilícitas , N-Metil-3,4-metilenodioxianfetamina , Adolescente , Adulto , Alcaloides , Anfetamina , Benzodiazepinas , Fármacos del Sistema Nervioso Central , Niño , Preescolar , Cromatografía Liquida , Heroína , Humanos , Lactante , Padres , Extractos Vegetales , Prevalencia , Psicotrópicos , Detección de Abuso de Sustancias , Espectrometría de Masas en Tándem
10.
Anal Bioanal Chem ; 400(1): 101-17, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21127842

RESUMEN

A library of collision-induced dissociation (CID) accurate mass spectra has been developed for efficient use of liquid chromatography in combination with hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) as a tool in systematic toxicological analysis. The mass spectra (Δm < 3 ppm) of more than 2,500 illegal and therapeutic drugs, pesticides, alkaloids, other toxic chemicals and metabolites were measured, by use of an Agilent 6530 instrument, by flow-injection of 1 ng of the pure substances in aqueous ammonium formate-formic acid-methanol, with positive and negative electrospray-ionization (ESI), selection of the protonated or deprotonated molecules [M+H](+) or [M-H](-) by the quadrupole, and collision induced dissociation (CID) with nitrogen as collision gas at CID energies of 10, 20, and 40 eV. The fragment mass spectra were controlled for structural plausibility, corrected by recalculation to the theoretical fragment masses and added to a database of accurate mass data and molecular formulas of more than 7,500 toxicologically relevant substances to form the "database and library of toxic compounds". For practical evaluation, blood and urine samples were spiked with a mixture of 33 drugs at seven concentrations between 0.5 and 500 ng mL(-1), prepared by dichloromethane extraction or protein precipitation, and analyzed by LC-QTOF-MS in data-dependent acquisition mode. Unambiguous identification by library search was possible for typical basic drugs down to 0.5-2 ng mL(-1) and for benzodiazepines down to 2-20 ng mL(-1). The efficiency of the method was also demonstrated by re-analysis of venous blood samples from 50 death cases and comparison with previous results. In conclusion, LC-QTOF-MS in data-dependent acquisition mode combined with an accurate mass database and CID spectra library seemed to be one of the most efficient tools for systematic toxicological analysis.


Asunto(s)
Alcaloides/análisis , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Plaguicidas/análisis , Preparaciones Farmacéuticas/análisis , Alcaloides/toxicidad , Humanos , Plaguicidas/toxicidad
11.
Proc Natl Acad Sci U S A ; 105(30): 10426-31, 2008 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-18663222

RESUMEN

For humans alcohol consumption often has devastating consequences. Wild mammals may also be behaviorally and physiologically challenged by alcohol in their food. Here, we provide a detailed account of chronic alcohol intake by mammals as part of a coevolved relationship with a plant. We discovered that seven mammalian species in a West Malaysian rainforest consume alcoholic nectar daily from flower buds of the bertam palm (Eugeissona tristis), which they pollinate. The 3.8% maximum alcohol concentration (mean: 0.6%; median: 0.5%) that we recorded is among the highest ever reported in a natural food. Nectar high in alcohol is facilitated by specialized flower buds that harbor a fermenting yeast community, including several species new to science. Pentailed treeshrews (Ptilocercus lowii) frequently consume alcohol doses from the inflorescences that would intoxicate humans. Yet, the flower-visiting mammals showed no signs of intoxication. Analysis of an alcohol metabolite (ethyl glucuronide) in their hair yielded concentrations higher than those in humans with similarly high alcohol intake. The pentailed treeshrew is considered a living model for extinct mammals representing the stock from which all extinct and living treeshrews and primates radiated. Therefore, we hypothesize that moderate to high alcohol intake was present early on in the evolution of these closely related lineages. It is yet unclear to what extent treeshrews benefit from ingested alcohol per se and how they mitigate the risk of continuous high blood alcohol concentrations.


Asunto(s)
Alcoholes/metabolismo , Polen/química , Consumo de Bebidas Alcohólicas , Intoxicación Alcohólica , Animales , Biomarcadores/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Fermentación , Flores , Cabello/metabolismo , Masculino , Mamíferos , Polinización , Tupaiidae
12.
Anal Bioanal Chem ; 396(7): 2469-77, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20145912

RESUMEN

Fatty acid ethyl esters (FAEE) and ethyl glucuronide (EtG) were determined in 602 meconium samples in a maternal health evaluation study for detection of gestational alcohol consumption. A validated headspace solid phase microextraction method in combination with GC-MS was used for FAEE and the cumulative concentration of ethyl palmitate, ethyl linoleate, ethyl oleate, and ethyl stearate with a cut-off of 500 ng/g was applied for interpretation. A new and simple method was developed and validated for quantification of EtG from 10-20 mg meconium with D(5)-EtG as internal standard consisting of 30 min. extraction with methanol/water (1:1, v/v), evaporation of methanol, filtration of the aqueous solution through a cellulose filter and injection into LC-MS-MS. The limits of detection and quantification for EtG were 10 and 30 ng/g, the recovery 86.6 to 106.4% and the standard deviation of the concentrations ranged from 13% at 37 ng/g to 5% at 46,700 ng/g (N = 6). FAEE above the cut-off were found in 43 cases (7.1%) with cumulative concentrations between 507 and 22,580 ng/g and with one outlier of about 150,000 ng/g (EtG not detected). EtG was detected in 97 cases (16.3%) and concentrations between LOD and 10,200 ng/g with another outlier of 82,000 ng/g (FAEE 10,500 ng/g). Optimal agreement between the two markers was obtained with a cut-off for EtG of 274 ng/g and 547 cases with both FAEE- and EtG-negative, 33 cases with both FAEE- and EtG-positive, nine cases with FAEE-positive and EtG-negative, and seven cases with FAEE-negative and EtG-positive. Differences in physical, chemical, and biochemical properties and in the pharmacokinetic behavior are discussed as reasons for the deviating cases. In none of the 602 cases, serious alcohol consumption was reported by the mothers and no evidence for gestational ethanol exposure was observed in the medical investigation of the newborns. It is concluded that the combined use of FAEE and EtG in meconium as markers for fetal alcohol exposure essentially increases the accuracy of the interpretation and helps to avoid false positive and false-negative results.


Asunto(s)
Alcoholismo/diagnóstico , Cromatografía Liquida/métodos , Ácidos Grasos/análisis , Glucuronatos/análisis , Meconio/química , Complicaciones del Embarazo/diagnóstico , Efectos Tardíos de la Exposición Prenatal/diagnóstico , Espectrometría de Masa por Ionización de Electrospray/métodos , Biomarcadores/análisis , Ésteres/análisis , Femenino , Humanos , Recién Nacido , Bienestar Materno , Embarazo
13.
Ann Neurol ; 64(1): 42-52, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18067175

RESUMEN

OBJECTIVE: Marijuana and alcohol are most widely abused drugs among women of reproductive age. Neurocognitive deficits have been reported in children whose mothers used marijuana during pregnancy. Maternal consumption of ethanol is known to cause serious developmental deficits METHODS: Infant rats and mice received systemic injections of Delta(9)-tetrahydrocannabinol (THC; 1-10mg/kg) or the synthetic cannabinoid WIN 55,212-2 (1-10mg/kg), alone or in combination with subtoxic and toxic ethanol doses, and apoptotic neurodegeneration was studied in the brains RESULTS: Acute administration of THC (1-10mg/kg), the principal psychoactive cannabinoid of marijuana, markedly enhanced proapoptotic properties of ethanol in the neonatal rat brain. THC did not induce neurodegeneration when administered alone. Neuronal degeneration became disseminated and severe when THC was combined with a mildly intoxicating ethanol dose (3gm/kg), with the effect of this drug combination resembling the massive apoptotic death observed when administering ethanol alone at much higher doses. The detrimental effect of THC was mimicked by the synthetic cannabinoid WIN 55,212-2 (1-10mg/kg) and counteracted by the CB(1) receptor antagonist SR141716A (0.4mg/kg). THC enhanced the proapoptotic effect of the GABA(A) agonist phenobarbital and the N-methyl-D-aspartate receptor antagonist dizocilpine. Interestingly, infant CB(1) receptor knock-out mice were less susceptible to the neurotoxic effect of ethanol. Furthermore, the CB(1) receptor antagonist SR141716A ameliorated neurotoxicity of ethanol INTERPRETATION: These observations indicate that CB(1) receptor activation modulates GABAergic and glutamatergic neurotransmission and primes the developing brain to suffer apoptotic neuronal death.


Asunto(s)
Envejecimiento/fisiología , Trastornos del Sistema Nervioso Inducidos por Alcohol/inducido químicamente , Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Cannabinoides/agonistas , Etanol/agonistas , Neurotoxinas/agonistas , Trastornos del Sistema Nervioso Inducidos por Alcohol/metabolismo , Trastornos del Sistema Nervioso Inducidos por Alcohol/fisiopatología , Animales , Animales Recién Nacidos , Benzoxazinas/agonistas , Benzoxazinas/toxicidad , Encéfalo/fisiopatología , Cannabinoides/toxicidad , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Depresores del Sistema Nervioso Central/agonistas , Depresores del Sistema Nervioso Central/toxicidad , Relación Dosis-Respuesta a Droga , Dronabinol/agonistas , Dronabinol/toxicidad , Resistencia a Medicamentos/efectos de los fármacos , Resistencia a Medicamentos/fisiología , Sinergismo Farmacológico , Etanol/toxicidad , Antagonistas de Aminoácidos Excitadores/toxicidad , Agonistas del GABA/toxicidad , Ratones , Ratones Noqueados , Morfolinas/agonistas , Morfolinas/toxicidad , Naftalenos/agonistas , Naftalenos/toxicidad , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Neurotoxinas/toxicidad , Ratas , Ratas Wistar , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/antagonistas & inhibidores
14.
Int J Legal Med ; 123(6): 517-9, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19621234

RESUMEN

We report the case of a 33-year-old man admitted to a psychiatric hospital because of paranoid schizophrenia. The man was found dead lying in his bed with the face pressed against a pillow and with elevated buttocks. The autopsy did not reveal a cause of death. The histological findings displayed the signs of the haemorrhagic-dysoric syndrome with acute emphysema; these findings are pathognomonic of obstructive asphyxia. The adverse effects of the neuroleptics demonstrated by the toxicological findings may have accelerated the loss of consciousness and facilitated the unusual position of the body. On the basis of the clinical history, the autopsy findings, the histological features and the toxicological results, asphyxia due to smothering was diagnosed as the cause of death.


Asunto(s)
Asfixia/etiología , Asfixia/patología , Ropa de Cama y Ropa Blanca , Adulto , Antipsicóticos/análisis , Clorprotixeno/análisis , Clozapina/análisis , Patologia Forense , Hemorragia/patología , Humanos , Macrófagos Alveolares/patología , Masculino , Posición Prona , Enfisema Pulmonar/patología , Psicología del Esquizofrénico
15.
Ther Drug Monit ; 31(2): 261-6, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19258930

RESUMEN

A serious challenge in diagnosing fetal alcohol spectrum disorder (FASD) is the need to document alcohol use during pregnancy. Maternal/paternal alcohol abuse affects the likelihood of fetal alcohol exposure, and hence the occurrence of FASD. The objective of the current study was to document the use of the fatty acid ethyl ester (FAEE) hair test, a biomarker of excessive alcohol use, in parents at risk of having children with FASD and quantify the prevalence of alcohol use in this population. Hair samples submitted for FAEE testing between October 2005 and May 2007 were evaluated (n = 324). Subjects consisted of the parents of at-risk children. Samples were analyzed using a previously published method. Briefly, samples underwent a liquid-liquid extraction, followed by headspace solid phase microextraction, and were then analyzed by gas chromatography-mass spectrometry using deuterated FAEE as internal standards. Limit of detection and limit of quantification values were between 0.01-0.04 ng/mg and 0.04-0.12 ng/mg, respectively. Positive levels for excessive drinking were ascertained using a cutoff level of 0.5 ng/mg, offering 90% sensitivity and specificity. The rate of positive hair samples for excessive drinking was 33.3% (32.4% among women and 35.4% among men) (n = 324). The majority of samples (62%) had cumulative FAEE levels above a level that excludes strict abstinence (0.2 ng/mg) and many (19%) were highly positive (above 1.0 ng/mg). Of 26 FAEE hair tests for which women were reported to be pregnant, 38% had FAEE hair levels above 0.2 ng/mg and 19% tested positive for excessive drinking, with levels above 0.5 ng/mg; 12% had levels above 1.0 ng/mg. The high rate of positive FAEE results demonstrates that the FAEE hair test corroborates the clinical suspicion of alcohol use in parents of children at risk for FASD. Our results suggest that FAEE hair analysis may be a powerful tool in detecting excessive alcohol use in the perinatal period.


Asunto(s)
Alcoholismo/diagnóstico , Ácidos Grasos/análisis , Trastornos del Espectro Alcohólico Fetal/etiología , Cabello/química , Complicaciones del Embarazo/diagnóstico , Detección de Abuso de Sustancias/métodos , Adolescente , Adulto , Anciano , Alcoholismo/complicaciones , Alcoholismo/metabolismo , Biomarcadores/análisis , Ésteres , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/metabolismo , Efectos Tardíos de la Exposición Prenatal/etiología , Factores de Riesgo , Adulto Joven
16.
Forensic Sci Int ; 297: 161-170, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30831411

RESUMEN

BACKGROUND: Hair samples from children are frequently analyzed in order to characterize their endangerment in a drug using environment. However, the interpretation of the results remains difficult because of lacking data for comparison. In this study, hair samples from families with drug consuming parents were analyzed for illegal and selected medical drugs and the results were evaluated concerning a relationship between findings of parents and children depending on kind of drug, age and gender of children as well as maternal or paternal drug concentrations in hair. METHODS: In an ongoing social supporting project for families with underage children and drug consuming parents, hair samples were analyzed since 2011 for methadone, opiates and opioid analgesics, cocaine, amphetamines, ecstasy, cannabinoids and benzodiazepines by LC-MS/MS with LOQs ≈ 0.01 ng/mg. From the data pool of more than 1300 individuals, 100 families with results for one or both parents and one to five children, 30 families with results only for both parents, and 11 families with results only for 2-4 children were selected. Fifty eight of these 141 families were repeatedly tested (altogether 251 family tests). RESULTS: One to 5 drugs were detected in 239 (95.2%) of the family tests with highest occurrence of cocaine (79.7%) and THC (50.2%). According to the concentrations of the tested persons, the most probable drug users were the mother (25%), the father (24%), both parents (16%), or were not tested (30%). Within the families, there was an agreement of the detected drugs between parents and children of 47.8%, between both parents of 36.1%, and between children of 42.3%. For parents with hair concentrations in the typical range of regular drug use, the drug was detected in children hair with the following frequency: methadone 65.5%, heroin (6-AM) 63.6%, cocaine 92.1%, amphetamine 80%, MDMA 42.9% and THC 67.4% with higher percentage for younger children. The agreement for medical drugs (benzodiazepines 7.7%, synthetic opioids 8.7%, diphenhydramine 7.1%) was much lower suggesting voluntary administration or intake. Despite the strong variation of the data, clear trends were found that the child/parent drug concentration ratio decreases with increasing children age and is higher for boys than for girls. CONCLUSION: The comparison of hair results within families gives a deeper insight in the drug situation, often enables the identification of the drug user and is helpful for social and legal decisions to improve the conditions of the children.


Asunto(s)
Familia , Cabello/química , Narcóticos/análisis , Detección de Abuso de Sustancias/métodos , Trastornos Relacionados con Sustancias/diagnóstico , Adulto , Factores de Edad , Niño , Protección a la Infancia , Hijo de Padres Discapacitados , Preescolar , Cromatografía Liquida , Femenino , Humanos , Lactante , Masculino , Espectrometría de Masas , Factores Sexuales
17.
Am J Obstet Gynecol ; 198(4): 407.e1-5, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18221928

RESUMEN

OBJECTIVES: The objective of the study was to investigate whether biomarkers of alcohol consumption would provide additional information to the use of a validated alcohol questionnaire in pregnant women. STUDY DESIGN: One hundred three pregnant women were included in the study. The women completed the Alcohol Use Disorders Identification Test (AUDIT) questionnaire, and a urine and hair sample was collected. The urine samples were used for determination of ethyl glucuronide (EtG) and ethyl sulfate and the hair samples for EtG and fatty acid ethyl esters (FAEE). RESULTS: Twenty-six women (25.2%) were identified as possible alcohol consumers by the combined use of AUDIT and direct ethanol metabolites. Seven subjects had EtG or FAEE levels in hair highly suspicious of heavy drinking, but only 1 of these were positive according to the AUDIT questionnaire CONCLUSION: The combined use of the AUDIT questionnaire and direct ethanol metabolites appear to identify more potential alcohol consumers among pregnant women than does the sole use of the AUDIT questionnaire.


Asunto(s)
Consumo de Bebidas Alcohólicas , Alcoholismo/diagnóstico , Etanol/orina , Ácidos Grasos/análisis , Cabello/química , Adulto , Alcoholismo/orina , Biomarcadores/análisis , Ésteres/análisis , Etanol/metabolismo , Femenino , Glucuronatos/análisis , Humanos , Proyectos Piloto , Embarazo , Encuestas y Cuestionarios , Suecia
18.
J Chromatogr B Analyt Technol Biomed Life Sci ; 846(1-2): 78-85, 2007 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-16971195

RESUMEN

A new method for determination of Delta(9)-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in hair based on alkaline hair hydrolysis, extraction by iso-octane, combined derivatization with N,O-bis-(trimethylsilyl)-trifluoroacetamide and headspace solid phase microextraction of the extract residue, and gas chromatography-mass spectrometry was developed and evaluated. The limits of detection of the three compounds were 0.01-0.02 ng/mg. The method was routinely applied to more than 250 hair samples. In 77 positive samples, the concentrations ranged from LOD to 4.2 ng/mg for THC (mean 0.49 ng/mg), to 12.1 ng/mg for CBD (mean 0.37 ng/mg) and to 0.85 ng/mg for CBN (mean 0.12 ng/mg) using a sample amount of 30 mg. The frequently observed increase of the segmental drug concentrations from proximal to distal is explained by progressive accumulation in the hair shaft from sebum or side stream smoke.


Asunto(s)
Cannabidiol/análisis , Cannabinol/análisis , Dronabinol/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Cabello/química , Calibración , Humanos , Estándares de Referencia , Sensibilidad y Especificidad
19.
Arch Kriminol ; 220(5-6): 141-51, 2007.
Artículo en Alemán | MEDLINE | ID: mdl-18260567

RESUMEN

Hyperthermia is one of the main symptoms of the toxic MDMA effect. In a fatal intoxication, the premortal increase in body temperature may lead to a false assessment of the time of death. The problems of drug-induced hyperthermia faced by forensic pathologists and criminal investigators are discussed on the basis of a death from the autopsy material of the Berlin Institute of Legal Medicine (CCM).


Asunto(s)
Fiebre/inducido químicamente , Drogas Ilícitas/envenenamiento , N-Metil-3,4-metilenodioxianfetamina/envenenamiento , Cambios Post Mortem , Adulto , Autopsia/legislación & jurisprudencia , Temperatura Corporal/efectos de los fármacos , Fiebre/patología , Humanos , Drogas Ilícitas/análisis , Masculino , N-Metil-3,4-metilenodioxianfetamina/análisis , Esquizofrenia/inducido químicamente , Esquizofrenia/patología
20.
Drug Test Anal ; 9(2): 323-326, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27004438

RESUMEN

Hygrine (HYG) and cuscohygrine (CUS) are natural alkaloids of coca leaves but are not found in illicit cocaine seizures. Therefore, they were proposed as markers for coca chewing in contrast to cocaine abuse in urine and hair testing. In order to examine at which step of the illegal cocaine production these compounds are lost, coca leaves were processed according to an authentic procedure by extraction with lime and kerosene, re-extraction with sulphuric acid, and precipitation of coca paste with ammonia. Non-extracted and extracted coca leaves, acidic extract and coca paste were analyzed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for cocaine, ecgonine methyl ester (EME), cinnamoylcocaine (CIN), HYG, and CUS. It follows from the results that under these conditions, HYG and CUS are extracted only to a minor extent by kerosene and are not precipitated from the acidic re-extract in the coca paste. Due to this behaviour in illegal cocaine production, they fulfil the conditions as markers for coca chewing in an optimal way. However, for unambiguous discrimination between coca chewing and cocaine abuse in human samples, additional markers of manufactured cocaine are required. Copyright © 2016 John Wiley & Sons, Ltd.


Asunto(s)
Acetona/análogos & derivados , Coca/química , Cocaína/análisis , Hojas de la Planta/química , Pirrolidinas/análisis , Acetona/análisis , Cromatografía Liquida , Cocaína/análogos & derivados , Trastornos Relacionados con Cocaína/diagnóstico , Cromatografía de Gases y Espectrometría de Masas , Humanos , Drogas Ilícitas/análisis , Masticación
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