The determination of psilocin and psilocybin in hallucinogenic mushrooms by HPLC utilizing a dual reagent acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence detection system

This paper describes a procedure for the determination of psilocin and psilocybin in mushroom extracts using high-performance liquid chromatography with postcolumn chemiluminescence detection. A number of extraction methods for psilocin and psilocybin in hallucinogenic mushrooms were investigated, with a simple methanolic extraction being found to be most effective. Psilocin and psilocybin were extracted from a variety of hallucinogenic mushrooms using methanol. The analytes were separated on a C12 column using a (95:5% v/v) methanol:10 mM ammonium formate, pH 3.5 mobile phase with a run time of 5 min. Detection was realized through a dual reagent chemiluminescence detection system of acidic potassium permanganate and tris(2,2'-bipyridyl)ruthenium(II). The chemiluminescence detection system gave improved detectability when compared with UV absorption at 269 nm, with detection limits of 1.2 x 10(-8) and 3.5 x 10(-9) mol/L being obtained for psilocin and psilocybin, respectively. The procedure was applied to the determination of psilocin and psilocybin in three Australian species of hallucinogenic mushroom.     

Quantification of psilocin in human whole blood using liquid chromatography–tandem mass spectrometry (LC–MS/MS)

There has been burgeoning interest in psilocybin-use for the treatment of various neurological and neurodegenerative diseases. Psilocybin is mistakenly perceived as the principal pharmacologically active compound due to its high concentrations found in magic mushrooms; however, it is the prodrug of psilocin. Despite the expanding body of clinical research seeking to understand the pharmacodynamic/pharmacokinetic properties of psilocin, and its role in inducing dramatic changes to cognitive function, there has not been a corresponding increase in the development of sensitive analytical methods that can quantify psilocin in different biological fluids. Existing analytical methods have been developed using plasma, serum, and urine as the matrix of choice, but with the unknown blood-to-plasma ratio of psilocin, any pharmacokinetic conclusions drawn solely on plasma data may be misleading. Thus, the main objective of this study is to develop the first analytical method that utilizes SPE and LC–MS/MS to quantify psilocin in human whole blood. The SPE procedure yielded a high recovery efficiency (≥89%) with minimal matrix effects. The method was validated according to ANSI/ASB 036 guidelines. Linearity was between 0.7–200 ng/mL and encompassed previously reported ranges found in plasma/serum. Bias, within- and between-run precision for all quality controls met ANSI/ASB 036 acceptability criteria. Endogenous/exogenous interferences and carryover were negligible. Psilocin stability was assessed at 4°C over 48 h and was considered stable. Although a proof-of-concept study will need to be performed to characterize the method, this analytical workflow was able to detect and quantify psilocin in human whole blood at low limits of quantification.     

法医毒物鉴定的发展及其问题分析

文章阐述了法医毒物鉴定在对象种类、适用检材、技术方法、应用领域和结果运用方面的发展趋势,分析了现阶段我国毒物鉴定实验室在规范建设、鉴定能力、技术系统和质量控制中存在的问题和缺陷,提出要通过加强鉴定机构及鉴定人的准入控制,建设一支高资质、高水平的队伍;通过执业监管、认证认可、水平测试和质量评估,保障毒物鉴定结果的可靠、准确.     

A study of drug detection in a postmortem pediatric population

At The Office of the Cuyahoga County Coroner (CCCO), Cleveland, Ohio, it is customary to perform an autopsy and conduct toxicological testing on decedents less than 19 years of age. This study provides a retrospective evaluation of drugs detected in a pediatric postmortem population between the years 1998 and 2002 (n = 730). Demographic information, cause and manner of death, and toxicological results were examined. Blacks comprised 54% of cases, males 59%, and 48% were less than one year of age or stillborn. Forty-two percent of deaths were ruled natural, 27% accident, 13% undetermined, 5% suicide, and 2% homicide. Of the 640 cases subjected to comprehensive testing, 38% of the cases were positive for at least one compound. Resuscitative/treatment drugs were detected most frequently (56% of positive results), followed by illicit drugs (26%), ethanol (11%), carbon monoxide (8%), and antihistamines (6%). Eighty-seven cases contained more than one drug. The deaths of 47 individuals were drug related (6%). In this population, it is recommended that illicit drugs and ethanol are targeted for testing, especially when limited specimens are available for analysis.     

毒物代谢动力学研究在法庭科学中的应用

随着法庭科学的发展以及近年来涉及毒品、毒物等中毒案件的增加,许多研究者对毒物代谢动力学进行研究,并取得了一定的成果.本文综述毒物代谢动力学研究及其在法庭科学中的应用状况,概要介绍毒物代谢动力学的研究现状、研究方法及研究成果,以期为相关研究及实践提供参考和借鉴.     

赛洛新和赛洛西宾分析方法研究进展

致幻剂是一类低剂量就使人意识、知觉和视觉异常,引起幻觉和情绪障碍的精神活性物质.赛洛新和赛洛西宾是一类具有致幻作用的色胺类化合物,存在于裸盖伞属和斑褶菇属的致幻蘑菇中.当前滥用及娱乐性使用含此类物质的致幻蘑菇的现象日趋严重,由此引起的危害公共安全案(事)件不断增多.因此,对于致幻蘑菇滥用的鉴定是当前司法鉴定领域的重要需...     

Possible role of pseudoephedrine and other over-the-counter cold medications in the deaths of very young children

The Philadelphia Medical Examiners Office has reported a series of 15 deaths between February 1999 and June 2005 of infants and toddlers 16 months and younger in which drugs commonly found in over-the-counter (OTC) cold medications were present. A total of 10 different drugs were detected: pseudoephedrine, dextromethorphan, acetaminophen, brompheniramine, carbinoxamine, chlorpheniramine, ethanol, doxylamine and the anticonvulsants, phenobarbital, and phenytoin. The drugs were confirmed and quantified by gas chromatography (GC)-mass spectrometry, with the exception of ethanol, which was analyzed by headspace GC and of phenobarbital and phenytoin that were quantified by GC with a nitrogen phosphorus detector. The most predominant drug was pseudoephedrine, which was found in all of the cases (blood concentration, n=14, range=0.10-17.0 mg/L, mean=3.34 mg/L) and was the sole drug detected in three cases. Acetaminophen was detected in blood from each of the five cases with sufficient sample. Other drugs (with frequency of detection) were dextromethorphan (five cases), carbinoxamine (four cases), chlorpheniramine (two cases) and brompheniramine, doxylamine, and ethanol (one case each). In the majority of the cases, toxicity from drugs found in easily available OTC medications was listed either as the direct cause of death or as a contributory factor. The manner of death was determined to be natural in only two of the cases. This postmortem study supports previous evidence that the administration of OTC cold medications to infants may, under some circumstances, be an unsafe practice and in some cases may even be fatal. The treating physicians and the general public need to be made more aware of the dangers of using OTC cold medications to treat very young children so that these types of tragedies might be avoided.     

Fatal mephenesin intoxication

This report describes a death related to the abuse of and intoxication by mephenesin. To the best of our knowledge, this is the first report case of lethal intoxication involving solely mephenesin and reporting mephenesin blood concentrations. The victim was a 48-year-old woman found unconscious at home. Resuscitation was unsuccessful. Toxicological analysis was performed on a blood sample collected during resuscitation. The results being negative, the body was exhumed for an autopsy, which revealed bronchial inhalation syndrome. Analysis in a second laboratory has revealed the presence of mephenesin in samples collected during autopsy. No other drug/toxin was found, and alcohol was negative. Reanalysis of the peripheral blood collected during resuscitation found a mephenesin concentration of 15.81 microg/mL (15-fold greater that the maximum concentration that would result from a single intake of a 500 mg formulation). The pathologist has concluded on a bronchial inhalation syndrome consecutive to a mephenesin overdose as the cause of death. The manner of this death is discussed in the light of the toxicological hair analysis and the medical past of the victim.     

Toxicology and Circumstances of Death of Homicide Victims in New South Wales, Australia 1996–2005

Abstract:  To determine the prevalence and circumstances of psychoactive substances amongst homicide victims, 485 consecutive cases autopsied at the NSW Department of Forensic Medicine (1/1/1996–12/31/2005) were analyzed. Substances were detected in 62.6% of cases, and illicit drugs in 32.8%. Alcohol, cannabis, opioids, and psychostimulants were most commonly detected. Alcohol and cannabis were both more prevalent amongst males. Mean ages were significantly younger for decedents who tested positive for a substance and for an illicit drug. Cases where death resulted from a physical altercation were more likely to have had alcohol and cannabis present. Illicit drugs were prominent amongst firearms deaths. The proportion of alcohol positive cases increased from 25.0% on Monday to 49.4% for Saturdays/Sundays. Alcohol was more common in incidents in the 0001–0600 h and 1800–2400 h periods. Psychoactive substances appear to substantially increase the risk of homicide, although there are important differences between drug classes in the circumstances of such incidents.     

Dextromethorphan abuse leading to assault, suicide, or homicide

Abstract: Dextromethorphan is a commonly encountered antitussive medication which has found additional therapeutic use in the treatment of pseudobulbar disorder and as an adjunct to opiate use in pain management. Dextromethorphan at high doses has phencyclidine‐like effects on the NMDA receptor system; recreational use of high doses has been found to cause mania and hallucinations. The toxicology and pharmacology of the drug in abuse are reviewed, and the historical literature of adverse psychiatric outcomes is assessed. Five new cases of dextromethorphan intoxication that resulted in assault, suicide, and homicide are reported, together with the corresponding toxicology results. Blood concentrations ranged from 300 to 19,000 μg/L. These results are compared with typical concentrations reported in therapeutic use and impaired driving cases. Based on these findings, dextromethorphan should be considered as a potential causative agent in subjects presenting with mania, psychosis, or hallucinations, and abusers are at risk for violent and self‐destructive acts.     

A fatal case of suspected anaphylaxis with cefoperazone and sulbactam: LC-MS analysis

Cefoperazone and sulbactam are prescribed in combination and used in the treatment of moderate to severe bacterial infections. Serious anaphylaxis is a rare side effect. This report describes a fatal case of suspected anaphylaxis after intravenous administration of a combination of the two drugs. Heart blood was analyzed for cefoperazone by protein precipitation with acetonitrile and by liquid-liquid precipitation for sulbactam after protein precipitation with aqueous acetonitrile, followed by tandem mass spectrometry in the product ion scan mode for identification and by liquid chromatography mass spectrometry in the selected ion monitoring mode for quantitation. Calibration curves for cefoperazone and sulbactam were linear over the range 0.07 to 1.93 and 0.046 to 0.914 microg/ml respectively. The decedent's blood concentrations of cefoperazone and sulbactam were 0.368 and 0.143 microg/ml respectively. As these concentrations were below concentrations reported after single dosing studies and below those considered to be minimally inhibitory, death was presumed to have been caused by hypersensitivity and not an overdose. In conclusion, this procedure is useful for detecting and quantitating cefoperazone and sulbactam in postmortem blood and may be useful in the evaluation of anaphylaxis.     

Fatality involving complications of bupivacaine toxicity and hypersensitivity reaction

This case represents unusual findings of elevated bupivacaine and tryptase concentrations following local anesthetic, bupivacaine, administered as a scalene nerve block for elective rotator cuff repair surgery. Following bupivacaine injection, the patient exhibited almost immediate seizure activity, bradycardia, and cardiac arrest. Resuscitative efforts including cardiopulmonary bypass restored a cardiac rhythm. However, the clinical medical status of the patient progressively declined and he died 7 h following administration of the local anesthetic. Autopsy revealed several abnormalities of the heart including cardiomegaly, myocardial bridging, and lipomatous hypertrophy of the intraatrial septum, which may have contributed to bradycardia and arrhythmia. Postmortem toxicology results revealed elevated bupivacaine and tryptase concentrations. Elevated postmortem bupivacaine concentrations 7 h following administration and abrupt onset of seizures indicate unintentional intravascular injection instead of nerve and tissue infiltration. An elevated postmortem tryptase concentration points to the possibility of a hypersensitivity reaction to bupivacaine.     

Concentrations of Opiates and Psychotropic Agents in Polydrug Overdoses: A Surprising Correlation Between Morphine and Antidepressants

Abstract: The relationship between postmortem concentrations of morphine and co‐detected psychoactive drugs in fatal overdoses is examined. Morphine and other drugs were detected in 161 medicolegal autopsy cases. Subsets of these morphine‐positive cases based on drug class were established, including opioids, antidepressants, ethanol, benzodiazepines, and “other.” Each subset was split into high or low concentration groups based on median drug concentrations. Morphine concentrations of the [high] and [low] groups were compared, with no significant difference in morphine concentration identified in the opioid, ethanol, or benzodiazepine subsets. The “other” drug class was too heterogeneous for statistical assessment. Morphine concentrations did show a significant direct relationship (p = 0.01) with antidepressants, namely increased concentrations of antidepressant drugs are associated with an increased concentration of morphine. This trend probably remains even after excluding cocaine‐positive cases. The unsuspected finding that postmortem concentrations of antidepressants positively correlate with morphine levels may be important in the treatment of depression in drug addicts.     

The forensic deaths caused by pesticide poisoning between the years 2006 and 2009 in Izmir, Turkey

Pesticide poisoning is still a significant health problem in Turkey. We conducted a retrospective study of autopsy cases at Izmir Branch of the Council of Forensic Medicine to describe the characteristics of deaths caused by pesticide poisoning between 2006 and 2009. The distributions of the cases according to gender and age were as follows: men 74.1% (n = 40, mean [±SD] age, 44.7 ± 14.1), women 25.9% (n = 14, mean [±SD] age, 39.2 ± 18.9). The majority of pesticide-poisoning deaths were suicides (n = 43, 80%) followed by accidents (n = 4, 8%) and homicide (n = 1, 2%). The manner of death could not be determined in six cases (11%). Suicides mostly occurred at home (n = 26, 63%) (p < 0.05). Methomyl was the most frequent pesticide (n = 9, 17%) among the all cases. This study reported that most of the pesticides found in poisoning cases were highly hazardous types. Combined efforts of medical professionals and law makers are needed for enacting strict laws against highly hazardous pesticides.     

Toxicology and characteristics of fatal oxycodone toxicity cases in New South Wales, Australia 1999-2008

All cases of fatal oxycodone toxicity presenting to the New South Wales Department of Forensic Medicine over the period January 1, 1999, to December 31, 2008, were retrieved. A total of 70 cases were identified. The mean age was 48.9 years, 58.6% were men, 21.4% were suicides, and in 30% oxycodone had not been prescribed to the decedent. Injecting drug users constituted 27.1% of cases, and oxycodone tablets were injected immediately prior to death by 21.4%. The mean blood oxycodone concentration was 0.40 mg/L (range 0.06-53.00 mg/L). In all cases, psychoactive substances other than oxycodone were also detected, most frequently hypnosedatives (68.6%), other opioids (54.3%), antidepressants (41.4%), and alcohol (32.9%). Preexisting systemic disease was common: cardiovascular (64.2%), pulmonary (49.3%), hepatic (66.7%), and renal (43.9%).