RESUMO
The consumption patterns of five categories of psychoactive substances (PS), including "conventional" illicit drugs, new psychoactive substances (NPS), therapeutic opioids, alcohol and nicotine, were studied in the city of Split, Croatia, using wastewater-based epidemiology (WBE), with an emphasis on the impact of a large electronic music festival. The study involved the analysis of 57 urinary biomarkers of PS in raw municipal wastewater samples collected in three characteristic periods, including the festival week in the peak-tourist season (July) and reference weeks in the peak-tourist season (August) and the off-tourist season (November). Such a large number of biomarkers allowed the recognition of distinct patterns of PS use associated with the festival, but also revealed some subtle differences between summer and autumn seasons. The festival week was characterized by markedly increased use of illicit stimulants (MDMA: 30-fold increase; cocaine and amphetamine: 1.7-fold increase) and alcohol (1.7-fold increase), while consumption of other common illicit drugs (cannabis and heroin), major therapeutic opioids (morphine, codeine and tramadol) and nicotine remained rather constant. Interestingly, NPS and methamphetamine clearly contributed to the festival PS signature in wastewater, but their prevalence was rather low compared to that of common illicit drugs. Estimates of cocaine and cannabis use were largely consistent with prevalence data from national surveys, whereas differences were found for typical amphetamine-type recreational drugs, particularly MDMA, and for heroin. The WBE data suggest that the largest proportion of morphine came from heroin consumption and that the percentage of heroin users seeking treatment in Split is probably rather low. The prevalence of smoking calculated in this study (30.6 %) was consistent with national survey data for 2015 (27.5-31.5 %), while the average alcohol consumption per capita >15 years (5.2 L) was lower than sales statistics suggest (8.9 L).
Assuntos
Cocaína , Drogas Ilícitas , Música , N-Metil-3,4-Metilenodioxianfetamina , Transtornos Relacionados ao Uso de Substâncias , Poluentes Químicos da Água , Humanos , Águas Residuárias , Nicotina/análise , Analgésicos Opioides/análise , Heroína/análise , Férias e Feriados , Drogas Ilícitas/análise , Anfetamina , Cocaína/análise , Etanol/análise , Detecção do Abuso de Substâncias , Poluentes Químicos da Água/análise , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
Heroin, a semisynthetic opioid drug synthesized from morphine, is the 3,6-diacetyl ester of morphine (diacetylmorphine). The post-mortem diagnosis of heroin-related death could be an issue and usually rely on a combination of investigations, including the autopsy, histological and toxicological analysis. We conducted the present study to evaluate the correlation between the heroin concentration in biological fluids (peripheral blood, bile and urine) and the post-mortem anti-6-MAM antibody expression in various tissues (brain, heart, lung, liver and kidney) using immunohistochemical staining. A quantitative analysis of the immunohistochemical reaction was carried out. 45 cases of heroin-related death investigated at the Forensic Pathology Institutes of the University of Rome, Foggia and Pisa were included. The control group was composed of 15 cases of death due to other causes, without brain lesions and negative toxicological analysis for drugs. We found a positive immunohistochemical reaction in different organs and it was related to the timing of heroin metabolization. No reaction was found in the control group. Our findings show that immunohistochemistry can be a valuable tool for the post-mortem diagnosis of acute heroin abuse. A better understanding of the timing of heroin's metabolism can be useful in the forensic field and for future therapeutic applications.
Assuntos
Dependência de Heroína , Heroína , Anticorpos , Heroína/análise , Heroína/metabolismo , Dependência de Heroína/diagnóstico , Humanos , Derivados da Morfina/análise , Derivados da Morfina/metabolismoRESUMO
Illicit drug use is a global problem imposing social, economic, and health burdens on society. Wastewater-based epidemiology is an approach based on calculating the consumption of substances in the target population by analyzing the concentrations of human metabolic excretion products of licit and illicit substances in wastewater. This study estimated the changes in illicit drugs (cocaine, amphetamine, methamphetamine, ecstasy (3,4-Methylenedioxymethamphetamine), heroin, and marijuana (THC)), alcohol, and nicotine consumption in Adana Province during Ramadan compared to normal periods using wastewater-based epidemiology. An overall decrease was observed during the Ramadan Period, most strongly for ecstasy (29%) followed by heroin (19%). For cocaine, the variation was the slightest (8.6%). The differences were statistically significant for ecstasy, heroin, nicotine, and alcohol but not for cocaine, amphetamine, methamphetamine, and marijuana. This study is the first to show changes in the use of illicit drugs, alcohol, and nicotine under the influence of religious beliefs. In addition, there is limited data about illicit drugs, alcohol and nicotine abusers/users in Ramadan. This study provides information on the literature on this subject.
Assuntos
Cannabis , Cocaína , Drogas Ilícitas , Metanfetamina , N-Metil-3,4-Metilenodioxianfetamina , Poluentes Químicos da Água , Humanos , Drogas Ilícitas/análise , Águas Residuárias/análise , Nicotina/análise , Detecção do Abuso de Substâncias , Heroína/análise , Poluentes Químicos da Água/análise , N-Metil-3,4-Metilenodioxianfetamina/análise , Metanfetamina/análise , Cocaína/análise , Anfetamina , EtanolRESUMO
BACKGROUND: It is unknown if targeted risk reduction counseling in the health care setting, after documented exposure to fentanyl, can affect behavior change to reduce risks and increase utilization of evidence-based overdose prevention strategies. METHODS: We conducted a retrospective analysis of results (7/2018-6/2019) from questionnaire-facilitated counseling by recovery coaches in the emergency department (ED) and primary care settings following disclosure of a urine toxicology positive for fentanyl. RESULTS: Seventy-five percent of N = 101 respondents were neither aware of nor expecting fentanyl in their substances of use. Fifty-three (70 %) of those initially unaware answered that learning about exposure to and the risks from fentanyl changed their thoughts about reducing or abstaining from use. A greater proportion of patients seen in the ED expressed desire to stop or reduce opioid use as compared to ambulatory clinic patients (91 % vs. 46 %, p < 0.001). Of those not already engaged in treatment, 18 % and 15 % were interested in medication and behavioural health treatment, respectively, and each of them indicated a change in thought based on the counseling. Forty-five percent of individuals not yet receiving naloxone endorsed interest in receiving it, and 22 % of all respondents were somewhat or very interested in access to safe consumption sites. CONCLUSION: This study suggests a novel clinical utility in toxicology screens to inform behavior in the setting of illicit fentanyl exposure. In addition to linkages to evidence-based treatment, linkages to harm-mitigating strategies associated with ongoing substance use may be critical to a comprehensive overdose prevention strategy in the clinical setting.
Assuntos
Fentanila/urina , Conhecimentos, Atitudes e Prática em Saúde , Dependência de Heroína/psicologia , Dependência de Heroína/urina , Adulto , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/urina , Overdose de Drogas/prevenção & controle , Overdose de Drogas/psicologia , Overdose de Drogas/urina , Serviço Hospitalar de Emergência/tendências , Feminino , Fentanila/análise , Heroína/análise , Heroína/urina , Dependência de Heroína/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Naloxona/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/psicologia , Transtornos Relacionados ao Uso de Opioides/urina , Estudos Retrospectivos , Comportamento de Redução do Risco , Inquéritos e Questionários , Adulto JovemRESUMO
Conventional gas chromatography - mass spectrometry (GC-MS) takes 20-40â¯min per sample, which is undesirably slow in any application if speed can be increased while still meeting analytical needs. In this study, we achieved reasonably good separations with full analysis cycle times of less than 1â¯min by combining for the first time low-pressure (LP) GC-MS with low thermal mass (LTM) resistive-heating for rapid temperature ramping and cooling of the capillary column. The analytical column is threaded into the LTM thin-walled metal tubing in an instrumental device known as "LTM Fast GC" that is mounted at the top of the gas chromatograph in a detector port. The column inlet and outlet are connected to the GC injector and MS transfer line as usual. For LPGC-MS, a 40â¯cm, 0.1â¯mm. i.d. uncoated flow restrictor capillary connected at the injector is coupled with a 2.6â¯m, 0.25â¯mm i.d., 0.25⯵m film thickness analytical column leading to the MS. Thus, the inlet operates at normal GC pressures, but the analytical column is under vacuum, which increases the optimal helium carrier gas flow velocity thereby increasing speed of full range separations while maintaining acceptable quality of chromatography. This column configuration in LTM-LPGC-MS trades a 64-fold gain in speed of analysis vs. standard GC-MS for a 4-fold loss in chromatographic peak capacity, thereby converting analysis time from minutes into seconds in common applications. For example, jet fuel containing fatty acid methyl esters (akin to biofuel) was separated in 25â¯s with <1â¯min full analysis cycle time. An EPA Method 8270 mixture of 76 analytes was also analyzed in <1â¯min full cycle time by LTM-LPGC-MS. Other examples include very fast analysis of heroin in a street drug powder and elucidation of a new organic synthetic compound. In this report, we describe and discuss the several advantageous and practical features of LTM-LPGC-MS, as well as its trade-offs.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Hidrocarbonetos/química , Ésteres/química , Ácidos Graxos/análise , Ácidos Graxos/química , Heroína/análise , Pressão , VácuoRESUMO
BACKGROUND: Methadone maintenance treatment (MMT) services have been used in China for treatment of heroin dependence. But no study has been conducted to assess the appropriateness of MMT distribution and the potential abuse of methadone in China. This study aims to do that through a nationwide estimation of methadone consumption in China via wastewater-based epidemiology and subsequently compare it with MMT data and level of heroin abuse. METHODS: Wastewater samples were collected from 53 wastewater treatment plants in 27 major cities that cover all geographic regions of China. Methadone and pure heroin consumptions were estimated based on influent concentrations of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), morphine and codeine. RESULTS: Drug residues were detected in most samples. The ratio of EDDP/methadone was around 2 in influents and methadone and EDDP loads were strongly correlated, indicating that they originated from human consumption. Both influent methadone and EDDP loads in Southwest and Northwest China were significantly higher than those in other regions. The highest estimated consumptions of methadone and heroin in China were 22.0⯱â¯2.1â¯mg/1000â¯in./d and 263.9⯱â¯115.9â¯mg/1000â¯in./d, respectively. There was a significant positive correlation between methadone and heroin consumptions. CONCLUSIONS: Consumption of methadone in China was primarily from MMT services. The use of methadone and heroin displayed a clear geographical pattern: it is higher in the western inland regions than in the eastern regions. This study has shown that the distribution of MMT services is reflective of the level of heroin abuse in different regions of China.
Assuntos
Analgésicos Opioides/análise , Dependência de Heroína/epidemiologia , Heroína/análise , Metadona/análise , Tratamento de Substituição de Opiáceos/tendências , Vigilância Epidemiológica Baseada em Águas Residuárias , Adulto , Analgésicos Opioides/uso terapêutico , China/epidemiologia , Cidades/epidemiologia , Feminino , Dependência de Heroína/tratamento farmacológico , Humanos , Masculino , Metadona/uso terapêutico , Tratamento de Substituição de Opiáceos/métodos , Águas Residuárias/análiseRESUMO
Resumen: Objetivo: Monitorear el consumo de drogas a través de la medición de sus metabolitos en aguas residuales. Material y métodos: Se obtuvieron muestras de 31 plantas de tratamiento de agua residual y de 95 sitios con poblaciones específicas (38 escuelas, 42 unidades de tratamiento de adicciones y 15 centros de readaptación social). Usando cromatografía líquida de ultra-alta resolución, se midieron nueve metabolitos de seis drogas. Resultados: Ocho de nueve metabolitos de drogas fueron identificados en aguas residuales. Los metabolitos de marihuana (THC-COOH), cocaína (benzoilecgonina) y metanfetamina fueron identificados en escuelas, centros de readaptación social y de tratamiento de adicciones. En Nuevo Laredo, Culiacán y Torreón se encontraron los consumos per cápita más elevados de cocaína, marihuana, anfetamina y metanfetamina. Conclusiones: El monitoreo del uso de drogas a través de aguas residuales es factible en México y podría constituir un sistema de vigilancia para identificar cambios de su consumo en el tiempo.
Abstract: Objective: Monitor drug use through wastewater metabolite measurement. Materials and methods: Wastewater samples were obtained from 31 wastewater treatment plants and 95 sites with specific populations (38 schools, 42 units of addiction treatment and 15 penitentiaries). Using ultra high liquid chromatography, we measured nine metabolites from six drugs. Results: Eight out of nine drug metabolites were identified in the samples. Marijuana (THC-COOH), cocaine (benzoylecgonine) and methamphetamine were identified in schools, centers of addiction treatment and penitentiaries. Nuevo Laredo, Culiacan and Torreon had the highest consumption of cocaine, marijuana, amphetamine and methamphetamine. Conclusions: Monitoring drug use through wastewater is feasible in Mexico and could constitute a surveillance system to identify changes in the time.
Assuntos
Humanos , Drogas Ilícitas/análise , Consumo de Água (Saúde Ambiental) , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Dronabinol/análise , Dronabinol/análogos & derivados , Cannabis/química , Estudos de Viabilidade , Cromatografia Líquida de Alta Pressão , Cidades/epidemiologia , Cocaína/análise , Cocaína/análogos & derivados , Serviços de Saúde Comunitária/estatística & dados numéricos , Purificação da Água , Heroína/análise , Metanfetamina/análise , México/epidemiologiaRESUMO
BACKGROUND: Detection of heroin use is among the major tasks for drug testing and can be best performed by using 6-acetylmorphine as the target analyte. This study was performed to document analytical findings in oral fluid after OF heroin intake. METHODS: The samples were from routine drug testing of patients in substitution treatment. The analytical investigation was made with a forensic accredited liquid chromatography-tandem mass spectrometry method. RESULTS: Out of 2814 samples, from 1875 patients, sent for routine drug testing, 406 contained one or more opiate in the drug screening when applying a cutoff limit of 1 ng/mL neat OF. Out of these 406, 314 had a measured 6-AM concentration in neat OF ≥ 1 ng/mL. The study demonstrated that 6-AM is a viable parameter in oral fluid drug testing with an about 80% sensitivity compared to using morphine and codeine as biomarkers. An additional value of using 6-AM is the confidence in concluding a heroin intake. The 6-AM concentrations varied between 1 and >1000 ng/mL, with a median value of 18.6 ng/mL. Heroin was measured in 35 samples with a median value of 0.72 ng/mL. The positive rate for opiates in urine and OF drug testing was the same, 13.5%, in similar populations of patients. CONCLUSIONS: 6-AM is a preferred parameter in OF drug testing for monitoring heroin use and makes OF drug testing for detecting heroin use more effective than urine drug testing when using highly sensitive mass spectrometry methods.
Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Dependência de Heroína/diagnóstico , Heroína/análise , Entorpecentes/análise , Detecção do Abuso de Substâncias/métodos , Biomarcadores/análise , Cromatografia Líquida/métodos , Codeína/análise , Feminino , Humanos , Masculino , Morfina/análise , Derivados da Morfina/análise , Tratamento de Substituição de Opiáceos , Saliva/química , Sensibilidade e Especificidade , Fatores de TempoRESUMO
Clandestine heroin laboratories have been a feature of the Malaysian illicit drug scene since soon after the abuse of heroin emerged in 1972. The first few clandestine heroin laboratories which synthesised heroin via the acetylation of imported morphine were uncovered in 1973 and 1977. By the mid-1980s, this type of laboratory was replaced by heroin-cutting laboratories whereby imported high-grade heroin was cut to street heroin. This was to meet the rising demand for the drug owing to the rapid escalation of the number of drug users. Over the years, the most significant change in the composition of the street heroin is the decrease in its purity from 30%-50% to 3%-5%. Caffeine has remained the major adulterant and chloroquine is detected in virtually all recent seizures.
Assuntos
Contaminação de Medicamentos , Dependência de Heroína/epidemiologia , Heroína/síntese química , Drogas Ilícitas/síntese química , Contaminação de Medicamentos/legislação & jurisprudência , Contaminação de Medicamentos/prevenção & controle , Heroína/efeitos adversos , Heroína/análise , Dependência de Heroína/diagnóstico , Humanos , Drogas Ilícitas/efeitos adversos , Drogas Ilícitas/análise , Malásia/epidemiologia , Singapura/epidemiologiaRESUMO
Confirmation or exclusion of recent heroin consumption is still one of the major challenges for forensic and clinical toxicologists. A great variety of biomarkers is available for heroin abuse confirmation, including various opium alkaloids (eg, morphine, codeine), street heroin impurities (eg, 6-acetylcodeine [6-AC], noscapine, papaverine) as well as associated metabolites (eg, 6-monoacetylmorphine [6-MAM], morphine glucuronides). However, the presence of most of these biomarkers cannot solely be attributed to a previous heroin administration but can, among other things, also be due to consumption of poppy seed products ('poppy seed defense'), opium preparations or specific medications, respectively. A reliable allocation is of great importance in different contexts, for instance in the case of DUID (driving under the influence of drugs) investigations, in driving licence re-granting processes, in workplace drug testing (WDT), as well as in post-mortem identification of illicit opiate use. Additionally, differentiation between illicit street heroin abuse and pharmaceutical heroin administration is also important, especially within the frame of heroin-assisted treatments. Therefore, analysis of multiple biomarkers is recommended when illicit opiate consumption is assumed to obtain the most reliable results possible. Beyond that, interpretation of positive opiate test results requires a profound insight into the great variety of biomarkers available and their validity regarding the alleged consumption. This paper aims to provide an overview of the wide variety of heroin abuse biomarkers described in the literature and to review them regarding their utility and reliability in daily routine analysis.
Assuntos
Dependência de Heroína/diagnóstico , Dependência de Heroína/metabolismo , Heroína/metabolismo , Detecção do Abuso de Substâncias/normas , Biomarcadores/análise , Codeína/análogos & derivados , Codeína/análise , Codeína/metabolismo , Glucuronídeos/análise , Glucuronídeos/metabolismo , Heroína/análise , Humanos , Derivados da Morfina/análise , Derivados da Morfina/metabolismo , Ópio/análise , Ópio/metabolismo , Reprodutibilidade dos Testes , Detecção do Abuso de Substâncias/métodosRESUMO
Heroin consumption in major cities across China was estimated for the first time via wastewater-based epidemiology. Influent and effluent wastewater samples were collected from 49 wastewater treatment plants (WWTPs) in 24 major cities that cover all the geographic regions of the country. Concentrations of morphine, 6-acetylmorphine, and codeine were measured. Near complete removal of morphine by wastewater treatment processes was observed, whereas removal rates of codeine were slightly lower. Morphine loads were much higher than codeine loads at most WWTPs in China, a trend opposite to that in many European countries. In addition, morphine and codeine loads were strongly correlated at most WWTPs, indicating morphine and codeine in wastewater were predominantly from the same source, street heroin. At WWTPs in Guangzhou and Shenzhen, codeine loads were considerably higher than morphine loads, consistent with previous reports of codeine abuse (e.g., as cough syrup) among middle and high school students in Guangdong province. Heroin consumption was derived based on morphine loads and taking into account therapeutic use of morphine and codeine, as well as contribution of codeine and acetylcodeine in street heroin. Highest heroin consumption was observed in northwestern and southwestern China. The average heroin consumption of the sampled cities was 64.6±78.7mg/1000inh/d. The nation-wide average heroin consumption was much lower than that of methamphetamine, consistent with seizure data and numbers of registered heroin and methamphetamine users in China.
Assuntos
Dependência de Heroína/epidemiologia , Detecção do Abuso de Substâncias , Águas Residuárias/análise , China/epidemiologia , Cidades , Codeína/análise , Heroína/análise , Humanos , Morfina/análiseRESUMO
A simple sample pre-treatment method based on solid phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) has been optimized and validated for the assessment of 15 residual solvents (2-propanol, 2-methylpentane, 3-methylpentane, acetone, ethyl acetate, benzene, hexane, methylcyclohexane, methylcyclopentane, m-xylene, propyl acetate, toluene, 1,2,4-trimethylbenzene, dichloromethane, and ethylbenzene) in seized illicit cocaine and heroin. DMSO and DMF as sample diluents were found to offer the best residual solvent transference to the head space for further adsorption onto the SPME fiber, and the developed method therefore showed high sensitivity and analytical recovery. Variables affecting SPME were fully evaluated by applying an experimental design approach. Best conditions were found when using an equilibration time of 5 min at 70 °C and headspace sampling of residual solvents at the same temperature for 15 min. Method validation, performed within the requirements of international guidelines, showed excellent sensitivity, as well as intra- and inter-day precision and accuracy. The proposed methodology was applied to 96 cocaine samples and 14 heroin samples seized in Galicia (northwestern Spain) within 2013 and 2014.
Assuntos
Anestésicos Locais/análise , Cocaína/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Heroína/análise , Drogas Ilícitas/análise , Entorpecentes/análise , Microextração em Fase Sólida/métodos , Limite de Detecção , Solventes/análise , Detecção do Abuso de Substâncias/métodosRESUMO
BACKGROUND: Identification of external contamination is a challenge in hair analysis. This study investigates metabolite ratios of hydromorphone to morphine and hydrocodone to codeine as indicators to distinguish contamination from heroin use provided that hydromorphone/hydrocodone intake is excluded. RESULTS: Hair samples after external contamination with street heroin proved to be negative for hydromorphone/hydrocodone. Hair samples from individuals with suspected street heroin use/contamination or opiate medication were analyzed for 6-monoacetylmorphine, morphine, acetylcodeine, codeine, hydromorphone and hydrocodone, and metabolite ratios of hydromorphone to morphine and hydrocodone to codeine were assessed. Hair samples from individuals with medicinal heroin/morphine/codeine use displayed significantly higher metabolite ratios than those with suspected street heroin use/contamination. CONCLUSION: Hydromorphone/hydrocodone are solely formed during body passage. Thus, metabolite ratios can be used to distinguish morphine/heroin use from external contamination.
Assuntos
Analgésicos Opioides/análise , Cabelo/química , Heroína/análise , Hidrocodona/análise , Hidromorfona/análise , Alcaloides Opiáceos/análise , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida/métodos , Feminino , Dependência de Heroína/diagnóstico , Humanos , Masculino , Morfina/análise , Derivados da Morfina/análise , Espectrometria de Massas em Tandem/métodosRESUMO
PURPOSE: Heroin has a half-life of 2-6 min and is metabolized too quickly to be detected in autopsy samples. The presence of 6-acetylmophine (6-AM) in urine, blood, or other samples is convincing evidence of heroin use by a decedent, but 6-AM itself has a half-life of 6-25 min before it is hydrolyzed to morphine, so 6-AM may not be present in sufficient concentration to detect in postmortem samples. Codeine is often present in heroin preparations as an impurity and is not a metabolite of heroin. Studies report that a ratio of morphine to codeine greater than one indicates heroin use. We hypothesize that the ratio of morphine to codeine in our decedents abusing drugs intravenously will be no different in individuals with 6-AM present than in individuals where no 6-AM is detected, and we report our study of this hypothesis. METHODS: All accidental deaths investigated by the Jefferson County Coroner/Medical Examiner Office from 2010 to 2013 with morphine detected in blood samples collected at autopsy were reviewed. Five deaths where trauma caused or contributed to death were excluded from the review. The presence or absence of 6-AM and the concentrations of morphine and codeine were recorded for each case. The ratio of morphine to codeine was calculated for all decedents. Any individual in whom no morphine or codeine was detected in a postmortem sample was excluded from further study. Absence or presence of drug paraphernalia or evidence of intravascular (IV) drug use was documented in each case to identify IV drug users. The proportion of the IV drug users with and without 6-AM present in a postmortem sample was compared to the M/C ratio for the individuals. RESULTS: Of the 230 deaths included in the analysis, 103 IV drug users with quantifiable morphine and codeine in a postmortem sample were identified allowing for calculation of an M/C ratio. In these IV drug users, the M/C ratio was greater than 1 in 98 % of decedents. When controlling for the absence or presence of 6-AM there was no statistically significant difference in the proportion of IV drug users when compared to non IV drug users with an M/C ratio of greater than 1 (p = 1.000). CONCLUSION: The M/C ratio in IV drug users, if greater than 1, is seen in deaths due to heroin toxicity where 6-AM is detected in a postmortem sample. This study provides evidence that a M/C ratio greater than one in an IV drug user is evidence of a death due to heroin toxicity even if 6-AM is not detected in the blood. Using the M/C ratio, in addition to scene and autopsy findings, provides sufficient evidence to show heroin is the source of the morphine and codeine. Listing heroin as a cause or contributing factor in deaths with evidence of IV drug abuse and where the M/C ratio exceeds 1 will improve identification of heroin fatalities, which will allow better allocation of resources for public health initiatives.
Assuntos
Codeína/análise , Heroína/análise , Derivados da Morfina/análise , Morfina/análise , Entorpecentes/análise , Detecção do Abuso de Substâncias/métodos , Toxicologia Forense , Meia-Vida , Heroína/química , Heroína/intoxicação , Dependência de Heroína/diagnóstico , Humanos , Entorpecentes/química , Entorpecentes/intoxicação , Mudanças Depois da Morte , Estudos Retrospectivos , Abuso de Substâncias por Via Intravenosa/sangue , Abuso de Substâncias por Via Intravenosa/urinaRESUMO
The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised. Following death rabbits were placed in a supine position at room temperature and divided into three groups namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h after death. Various samples which included femoral blood, cardiac blood, lung, liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone marrow and skeletal muscle were taken. The samples were analysed with a validated LC-MS/MS method. It was observed that within minutes there was a significant increase in free morphine postmortem femoral blood concentration compared to the antemortem sample (0.01 ± 0.01 to 0.05 ± 0.02 mg/L).Various other changes in free morphine and metabolite concentrations were observed during the course of the experiment in various tissues. Principal component analysis was used to investigate possible correlations between free morphine in the various samples. Some correlations were observed but gave poor predictions (>20 % error) when back calculating. The results suggest that rabbits are a good model for further studies of postmortem redistribution but that further study and understanding of the phenomena is required before accurate predictions of the blood concentration at the time of death are possible.
Assuntos
Derivados da Morfina/farmacocinética , Morfina/farmacocinética , Entorpecentes/farmacocinética , Mudanças Depois da Morte , Tecido Adiposo/química , Animais , Medula Óssea/química , Cromatografia Líquida , Toxicologia Forense , Heroína/análise , Heroína/farmacocinética , Rim/química , Fígado/química , Pulmão/química , Espectrometria de Massas , Modelos Animais , Morfina/análise , Derivados da Morfina/análise , Músculo Esquelético/química , Entorpecentes/análise , Análise de Componente Principal , Coelhos , Corpo Vítreo/químicaRESUMO
In this study, an incubation, solid-phase extraction (SPE) and LC-MS-MS procedure was developed, validated and used for simultaneous analysis of amphetamine (AP), methamphetamine (MA), morphine (MOR), codeine (COD), 6-acetylmorphine (6-AM) and 6-acetylcodeine (6-AC) in hair. Hair samples were initially cut into sections, washed with dichloromethane, then sonicated in a methanol-trifluoroacetic acid mixture. The resulting solutions were processed with a SPE procedure before undergoing LC-MS-MS analysis. Mass spectrometric analysis was performed in positive-ion, multiple reactions monitoring (MRM) mode, using appropriate collision energy for each selected precursor ion. The overall protocol, when applied to the analysis of hair (50 mg) samples fortified with 100-10,000 pg/mg of the analytes, was found to achieve 55.5-74.6% recovery of the six analytes with the following analytical parameters: (i) intra- and interday precision/accuracy data for the six analytes in the 1.6-7.6%/-6.0-12.8% and 1.3-6.6%/-6.9-9.3% ranges, respectively; (ii) r(2) > 0.998 for all six analytes and (iii) LOD 2 pg/mg for AP and MA, and 8 pg/mg for MOR, COD, 6-AM and 6-AC; LOQ 10 pg/mg for all six analytes. This method was then utilized to (i) analyze hair samples collected from 86 self-reported drug users and (ii) evaluate the deposition pattern of drugs in head hairs from four female MA and heroin users in a rehabilitation facility. This relatively simple protocol was found superior over the GC-MS methods we have previously developed and utilized in our laboratory for the analysis of these six analytes.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Anfetaminas/análise , Cromatografia Líquida de Alta Pressão , Toxicologia Forense/métodos , Cabelo/química , Dependência de Heroína/metabolismo , Heroína/análise , Detecção do Abuso de Substâncias/métodos , Espectrometria de Massas em Tandem , Transtornos Relacionados ao Uso de Anfetaminas/diagnóstico , Calibragem , Cromatografia Líquida de Alta Pressão/normas , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Dependência de Heroína/diagnóstico , Humanos , Limite de Detecção , Modelos Lineares , Valor Preditivo dos Testes , Padrões de Referência , Reprodutibilidade dos Testes , Extração em Fase Sólida , Detecção do Abuso de Substâncias/normas , Espectrometria de Massas em Tandem/normasRESUMO
BACKGROUND: Heroin abuse is a significant public health issue and is on the rise because of the unintended consequences of strengthening controls for nonmedical use of prescription pain killers. Included in this trend is an increase in opiate exposed newborns that are particularly vulnerable to a number of negative health outcomes. METHODS: After presenting a fully validated liquid chromatography-tandem mass spectrometric method for codeine, morphine, 6-monoacetylmorphine, and meconin, a metabolite of the heroin contaminant noscapine, we compared the outcome of 46 authentic umbilical specimens with the results generated using a previous less sensitive method that did not include meconin. Additionally, we provided a summary of opiate finding from a year-long survey of specimens received into a commercial reference laboratory. RESULTS: The limits of detection for all 4 compounds were 0.1 ng/g, the limit of quantitation was 0.2 ng/g, and the assay was linear from 0.2 to 10.0 ng/g. Of the 46 comparative specimens, this method improved the identification of heroin exposure from 2 to 5, and the year-long survey identified 86 heroin-exposed newborns with 11 of them identified by the sole identification of meconin. CONCLUSIONS: This study demonstrated that a more sensitive analytical platform and the inclusion of meconin in the opiates assay improved the ability to distinguish between in utero heroin exposure and maternal administration of codeine or morphine.
Assuntos
Analgésicos Opioides/análise , Codeína/análise , Heroína/análise , Derivados da Morfina/análise , Morfina/análise , Noscapina/análogos & derivados , Cordão Umbilical/química , Adulto , Calibragem , Cromatografia Líquida de Alta Pressão , Feminino , Dependência de Heroína/diagnóstico , Dependência de Heroína/metabolismo , Humanos , Recém-Nascido , Noscapina/análise , Gravidez , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes , Extração em Fase Sólida , Detecção do Abuso de Substâncias , Espectrometria de Massas em TandemRESUMO
INTRODUCTION: Females who have developed addiction to heroin also abuse it during pregnancy. Heroin can be detected in the fetal blood-flow already an hour after maternal i.v. injection. Heroin metabolites enter the fetal blood-flow through the placental barrier by passive transport. CASE OUTLINE: We present a 27-year-old female in the 5th month of pregnancy that had a miscarriage. Chemo-toxicological analysis (gas chromatography with mass spectrometry--GC/MS), showed the presence of morphine in the fetal liver (31.92 ng/g), placenta (27.94 ng/g) and meconium (136.33 ng/g). The analysis did not show the presence of 6-monoacetylmorphine. CONCLUSION: In all cases when the autopsy of fetus or newborn is performed, with mother suspected as i.v. heroin abuser, chemo- toxicological placental analysis, placenta and meconium should be also done.
Assuntos
Morte Fetal , Dependência de Heroína , Heroína/análise , Morfina/análise , Morfina/isolamento & purificação , Entorpecentes/análise , Adulto , Autopsia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Recém-Nascido , Fígado/química , Fígado/embriologia , Mecônio/química , Derivados da Morfina/análise , GravidezRESUMO
Brain distribution pattern of "street" heroin metabolites (morphine and codeine) was investigated in two fatalities due to "acute narcotism". A suitable sample pretreatment prior to solid-phase-extraction was developed to achieve a good recovery of the analytes and to eliminate the interfering species. After derivatization with MSTFA, samples were analyzed by GC/MS. Specificity, accuracy, precision and linearity of the method were evaluated; LOD and LOQ were, respectively, 10ng/25ng for morphine and 5ng/10ng for codeine. This method was applied to the analysis of six brain areas (hippocampus, frontal lobe, occipital lobe, nuclei, bulb and pons) coming from two cases of heroin-related deaths. No evidence of accumulation of metabolites in a specific brain region was found.
Assuntos
Encéfalo/metabolismo , Codeína/análise , Heroína/análise , Drogas Ilícitas/análise , Morfina/análise , Detecção do Abuso de Substâncias/métodos , Adulto , Codeína/metabolismo , Overdose de Drogas/diagnóstico , Overdose de Drogas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Heroína/farmacocinética , Dependência de Heroína/diagnóstico , Dependência de Heroína/metabolismo , Humanos , Drogas Ilícitas/farmacocinética , Limite de Detecção , Masculino , Estrutura Molecular , Morfina/metabolismo , Reprodutibilidade dos Testes , Distribuição TecidualRESUMO
Apart from routine analysis of total morphine content required by the criminal justice system, quantification of other major components in illicit heroin has not been considered by the Malaysian enforcement laboratory. In order to quantify various other cutting agents in addition to alkaloids, a gas chromatographic (GC) method was developed to facilitate simultaneous quantification of eight target analytes commonly found in illicit heroin seized in Malaysia within a 12 min run time. The validation results demonstrated high selectivity with the use of an HP Ultra 2 capillary column. Different solvents were studied and methanol:chloroform (1:9) proved best for sample dissolution. The method was repeatable and reproducible. The study ranges covering 50-150% of the preferred concentrations of the eight analytes obtained r(2)>0.9997. Limits of detection up to 6µg/mL were also obtained and the method achieved 99-102% recovery. The capability of the method in heroin profiling was verified using samples from ten case samples.