卡西酮、甲卡西酮和4-甲基甲卡西酮的 LC-MS/MS分析方法的研究

目的 建立卡西酮、甲卡西酮、4-甲基甲卡西酮的LC-MS/MS定性定量分析方法.方法 采用Agilent 6460三重串联四极杆液质联用仪（LC/QQQ）,样品用甲醇直接提取,采用Agilent Zorbax（R）Eclipse Plus C18色谱柱（100mm×2.1mm,1.8μm）,流动相为0.1％甲酸和乙腈,梯度洗脱,流速为0.3mL/min,进样体积为3μL.质谱应用ESI源、正离子模式、多反应监测（MRM）方式检测卡西酮、甲卡西酮、4-甲基甲卡西酮.结果 卡西酮的线性范围为1ng/mL～25000ng/mL,甲卡西酮的线性范围为0.1ng/mL～～10000ng/mL,4-甲基甲卡西酮的线性范围为1ng/mL～10000ng/mL.结论 该方法简单、准确,灵敏度高,可以满足案件鉴定工作的需要.     

HPLC-MS/MS法检测血液中甲卡西酮及其代谢物

目的 建立同时检测血液中新精神活性物质甲卡西酮及其代谢物卡西酮、麻黄碱和伪麻黄碱含量的高效液相色谱-串联质谱方法 ,验证甲卡西酮在大鼠体内的代谢物.方法 血液样品中加入内标物甲卡西酮-D3,经甲醇提取后采用InfinityLab Poroshell 120 Chiral-V型色谱柱分离,以甲醇和乙腈混合流动相恒比洗脱,...     

“Bath Salts” the New York City Medical Examiner Experience: A 3‐Year Retrospective Review

“Bath salts” are synthetic derivatives of cathinones, compounds found in the leaves of Catha edulis, which possesses amphetamine‐like properties. At the New York City Office of Chief Medical Examiner, we conducted a 3‐year retrospective analysis of deaths in which cathinones were detected. Two categories emerged; those in which cathinones were a contributory cause of death (15 cases) and those in which they were an incidental finding (15 cases). Of the former group, 13 were associated with additional intoxicants; two deaths were attributed solely to cathinone intoxication, both survived 10 h: a man whose postmortem blood methylone concentration was 0.71 mg/L and a woman whose postmortem blood ethylone concentration was 1.7 mg/L. In the latter category, there were several individuals who had higher concentrations of cathinones than the above two, the highest being a blood methylone of 4.8 mg/L. Based upon our data and the literature presented, lethal concentrations of cathinones cannot be established.     

甲卡西酮对大鼠血浆代谢谱变化研究

目的 应用代谢组学技术研究腹腔注射甲卡西酮大鼠血浆代谢谱的变化,筛选出可用于甲卡西酮吸毒法医学鉴定的入体生物标志物.方法 SD大鼠随机分成低剂量甲卡西酮组(腹腔注射甲卡西酮溶液3mg/kg)、中剂量甲卡西酮组(腹腔注射甲卡西酮溶液12mg/kg)和对照组(腹腔注射等量生理盐水),注射3min后收集大鼠眼眶血,应用超高效...     

Suicide with acetylsalicylic acid

The authors report on a suicide of a 41-year-old man with acetylsalicylic acid. According to his own statement the man had taken about 200 tablets of Aspirin (65 g acetylsalicylic acid) and initially showed no symptoms of intoxication. 4-5 hours after ingestion he vomited twice, but clear intoxication symptoms like convulsions and cardiac arrhythmia occurred not earlier than 11 hours after ingestion. Resuscitation by the emergency physician was not successful. The chemical-toxicological analysis (HPLC-DAD) of blood samples taken in the hospital approximately 12 h after ingestion showed salicylate in concentrations of 475 mg/L to 557 mg/L. The post-mortem concentrations of salicylate were within the lethal-toxic range, i.e. 762 mg/L in heart blood and 215 mg/L in femoral blood. All tested organs contained equally lethal salicylate levels (e.g. 503 mg/L in the liver and 251 mg/L in the brain).     

Drunk Person Screening using Eye Thermal Signatures

Temperature distribution on the eyes of drunk persons is studied by means of thermal infrared images. The sclera and the iris are of the same temperature for the sober person, while for the intoxicated person, the sclera temperature increases. Consequently, only the thermal images from the drunk persons are necessary for intoxication screening. Forty‐one participants drank in a controlled alcohol consumption procedure. Their breath alcohol concentration was above the threshold of 0.2 mg/L of exhaled air, which corresponds to about 0.5 mg of alcohol per cubic centimeter of blood. Histogram modification algorithms were employed to prove that for 36 among the 41 intoxicated persons, the sclera becomes hotter. The Student t‐test verified with over 99% confidence the drunk discrimination capabilities of the procedure. The forensic science potential contribution of the method is that face infrared imagery is available to the authorities for supporting intoxication in case of criminal actions.     

Hypothermia and undressing associated with non-fatal bromazepam intoxication.

A 42-year-old woman with a history of depression was found unconscious, lying near her car in an early autumn morning. The lower part of her body was undressed and there were multiple purple spots and excoriations on the body suggesting at first a sexual assault. On admission to the intensive care unit, she presented a hypothermia with a central temperature of 28.4 degrees C. The biological samples obtained at the hospital were analysed. Blood concentration of bromazepam was 7.7 mg/l, which is above the highest level reported till now in a case of fatal intoxication.     

Determination of cathinone,cathine and norephedrine in hair of Yemenite khat chewers

A sensitive and reproducible method for the quantitative determination of cathinone (CTN), norpseudoephedrine (NPE, cathine) and norephedrine (NE) from hair was developed. The compounds were extracted for 4 hours with phosphate buffer pH 2.0, followed by a standard solid phase extraction procedure on a mixed phase column, derivatization with heptafluorobutyric anhydride (HFBA) and GC-MS separation and quantification using D(3)-ephedrine (D(3)-E) and alpha-aminoacetophenone (AAP) as the internal standards. The diastereomers NPE and NE were satisfactorily separated. In the validation, the limits of detection and of quantification were determined at 0.03-0.08 ng/mg and 0.10-0.24 ng/mg, respectively and the interday standard deviation was between 10 and 15%. The method was applied to hair samples of 24 Yemenite khat chewers. All three compounds were detected in 23 of these cases. The concentrations ranged from 0.57 to 23.9 ng/mg for NPE, 0.19-25.0 ng/mg for NE and 0.11-22.7ng/mg for CTN. A highly significant correlation was found between the self-reported data about the khat consumption habits of the volunteers (4-56h chewing per week) and the concentrations of norephedrine and norpseudoephedrine in hair.     

Fatal intoxication with tianeptine (Stablon)

Tianeptine (Stablon), although structurally similar to tricyclic antidepressants, acts by enhancing the reuptake of serotonin. A fatal case is presented involving a 26-year-old man, found lying in bed with a "mushroom of foam" around his mouth. Empty blister packs of Stablon and a suicide note were found next to the body. A liquid-liquid extraction procedure with n-hexane: ethyl acetate and n-hexane: 2-propanol, followed by LC-DAD-MS analysis, using positive mode electrospray ionization was performed. The detection limit was 0.001 microg/mL. The toxicological results revealed the following tianeptine concentrations in the post-mortem samples: blood 5.1 microg/mL; urine 2.0 microg/mL; liver 23 microg/g; stomach contents 22 mg. Femoral blood analyses also revealed an ethanol concentration of 0.53 g/L. The present method was also developed and validated for the other post-mortem specimens, since no previous published data had confirmed the post-mortem distribution of tianeptine. The absence of other suitable direct causes of death (macroscopic or histological) and the positive results achieved with the toxicological analysis led the pathologist to rule that death was due to an intoxication caused by the suicidal ingestion of tianeptine in combination with alcohol.     

The Characterization of 3,4-Dimethylmethcathinone (3,4-DMMC)

Analogs and derivatives of traditional illicit drugs are ever increasing in variety and creativity. Staying abreast of the new developments is a constant challenge for every forensic laboratory. Recently, a seizure from Australian Customs Service presented our laboratory with the designer cathinone 3,4-dimethylmethcathinone (3,4-DMMC). Gas chromatography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and ultraviolet (UV) spectrophotometry were employed to analyze the spectroscopic characteristics of this cathinone. As an analog, 3,4-DMMC exhibits similar if not identical IR and UV profiles to mephedrone (4-MMC) and methcathinone; however, the retention time from GC is unique as expected, and the electron impact fragmentation pattern is consistent with the fragmentation pattern of other cathinones. The chemical shifts of the carbons and hydrogens were assigned by both one- and two-dimensional NMR techniques, while the molecular weight was confirmed by LC/MS.     

Detection of diphenhydramine in autolytic brain tissue in poison-induced brain death syndrome

A case of accidental monointoxication caused by diphenhydramine is reported. Having taken 12 dragées of Neo-Emedyl (50 mg diphenhydramine), an 18-month-old girl showed the following symptoms: generalized erythema, dyspnoea, vomiting, hyperpyrexia, tremor, convulsions, coma, respiratory arrest and absence of reflexes. Computed tomography (CT) suggested a massive cerebral oedema. Her electroencephalogram was abnormally diffused at first; later on, it flattened significantly and became isoelectric between the 14th day and the final stoppage of circulation (after 5 weeks). Autopsy revealed total necrosis of the brain, with the venous cerebral blood vessels being thrombosed (the morphological basis for dissociated cerebral death). In autolysed brain tissue, diphenhydramine was detected at a concentration of 30 ng/g by GC/MS (gas chromatography, mass spectrometry); the concentration of the substance was less than 10 ng/g in the liver. The relatively high concentration in the brain was due to the previous blocking of the circulation. Cerebral death syndrome caused by intoxication offers the chance of detecting measurable amounts of the unchanged drug in autolysed brain tissue.     

Concentrations of zolpidem and zopiclone in venous blood samples from impaired drivers compared with femoral blood from forensic autopsies

The concentrations of zolpidem and zopiclone were determined in peripheral blood samples in two forensic materials collected over a 10-year period (2001-2010). The z-hypnotics were determined in venous blood from living subjects (impaired drivers) and in femoral blood from deceased persons (forensic autopsies), with the latter classified as intoxication or other causes of death. The z-hypnotics were determined in blood by capillary column gas chromatography (GC) with a nitrogen-phosphorous (N-P) detector after solvent extraction with n-butyl acetate. The analytical limit of quantitation (LOQ) was 0.02mg/L for zopiclone and 0.05mg/L for zolpidem and these have remained unchanged throughout the study. When death was attributed to drug intoxication (N=918), the median concentration of zopiclone in blood was 0.20mg/L compared with 0.06mg/L for other causes of death (N=1215) and 0.07mg/L in traffic offenders (N=691) (p<0.001). Likewise, a higher median concentration (0.30mg/L) was found in intoxication deaths involving zolpidem (N=357) compared with 0.13mg/L for other causes of death (N=397) or 0.19mg/L in impaired drivers (N=837) (p<0.001). Median concentration in blood of both z-hypnotics were appreciably higher in intoxication deaths when no other substances were identified; 0 70mg/L (N=12) for zopiclone and 1.35mg/L (N=12) for zolpidem. The median concentrations of z-hypnotics in blood decreased as the number of co-ingested substances increased for intoxication deaths but not other causes of death. The most prevalent co-ingested substances were ethanol in autopsy cases and diazepam in the motorists. This large compilation of forensic cases should prove useful when toxicologists are required to interpret concentrations of z-hypnotics in blood samples in relation to cause of death.     

Tissue distribution of olanzapine in a postmortem case

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.     

Fatal Overdose of Gamma‐hydroxybutyrate Acid After Ingestion of 1,4‐Butanediol

We report a case of fatal intoxication from 1,4‐butanediol (1,4‐BD), which was ingested by a young and “naïve” gamma‐hydroxybutyrate (GHB) consumer during a party with the co‐ingestion of alcohol, cannabis, and methylene‐dioxy‐methamphetamine. The following drug concentrations were found using gas chromatography coupled with mass spectrometry on autopsy samples and on a cup and a glass found at the scene: 20,350 mg/L (bottle) for 1,4‐BD; 1020 mg/L (femoral blood), 3380 mg/L (cardiac blood), 47,280 mg/L (gastric content), and 570 mg/L (vitreous humor) for GHB. The concentration of GHB is difficult to interpret in forensic cases due to the possibility of an endogenous production of GHB. The variable tolerance of the user may also modify the peri‐ and postmortem GHB concentrations. This case underscores the need to have many different sources of toxicology samples analyzed to avoid the hypothesis of endogenous production of GHB.     

Fatal intoxication by Remoxipride

The case history and toxicologic findings of a 23-year-old woman who committed suicide with Remoxipride are described. Remoxipride is a recently developed neuroleptic drug of the benzamide type. Remoxipride was detected in the liver, stomach content, blood, and urine. The concentration of Remoxipride in the blood was 230 mg/L. The recommended therapeutic level for Remoxipride should not exceed 7 to 8 mg/L. The victim had no blood alcohol, but an ethanol concentration of 0.048 g/100 L was detected in the urine. The mechanism of death from Remoxipride intoxication is not known. In clinical studies, sinus bradycardia and infrequent supraventricular and ventricular ectopic beats have been noted.     

Case report of a fatal intoxication by citalopram

Citalopram is an antidepressant drug within the group of the selective serotonin reuptake inhibitors (SSRI). It is widely prescribed both in Europe and in United States, and it has always been considered a "safe" drug as pure intoxication with lethal outcome is rare, and most cases of overdose, even with high doses of citalopram ingested, are reported to have an uneventful course.We report the case of a young woman found dead at home. She had been prescribed citalopram by her family doctor 3 weeks before her death for a depressive syndrome. Police found in her house 3 empty blister packages of 28 citalopram tablets (20 mg) and 2 bottles of citalopram oral solution (4%, 15 mL each). The autopsy findings were unremarkable. Nasal swabs, blood from femoral vein, urine, bile and tissue samples were collected for toxicologic investigation. Citalopram separation was performed by solid/liquid method, using Bond-Elute columns. The extracts were analyzed by GLC and GC/MS methods. The toxicologic analysis showed high levels of citalopram in all the examined fluids and tissue samples (blood concentration: 11.60 mg/L). No other drugs and alcohol were detected. Our data confirm that if no other drug is involved, fatal complications occur only after ingestion of very high doses. However, there is no predefined "toxic dose," and the conditions under which the overdose occurs can be very important. We report the exact concentrations of the citalopram in the organs, and wethink that this can be useful in the cases where the blood samples were not available (ie, carbonized or decomposed body).     

Driving under the influence of khat--alkaloid concentrations and observations in forensic cases

The use of the herbal stimulant khat (Catha edulis FORSK) is maintained by immigrants from countries where it is part of their cultural life (Arabian Peninsula and eastern Africa). In western countries the drug and its effects are largely unknown and no experience in evaluating impairment symptoms due to the khat-alkaloids, e.g. cathinone, cathine and norephedrine exists. Blood and urine samples from khat users involved in 19 cases of suspected driving under the influence of drugs were analysed and correlated with the results of medical examination and police officer reports. In 3 cases impaired driving and in 10 cases marked impairment of psychophysical functions was observed such as effects on the nervous system (slow pupil reaction to light, dry mouth, increased heart-rate), trembling, restlessness/nervousness, daze/apathy/dullness, impairment of attention, walking and standing on one leg. However, the alkaloid concentrations assayed in blood did not correlate with the impairment symptoms. Apart from an acute phase of indirect sympathomimetic action the development of habituation and withdrawal symptoms must also be considered in explaining the diversity of effects observed. From these results it can be concluded that chewing khat may severely impair driving ability, but may also be without noticeable effects.     

Survival of Very High Blood Alcohol Concentration Without Consequential Damage in a Patient Without a Previous Substance Use Disorder

Intoxications with alcohol may lead to death depending on (maximum) blood alcohol concentration (BAC) and accompanying factors such as liver function, tolerance, and comedication. Death may occur due to ethanol‐induced respiratory depression and/or aspiration of gastric content (due to an impaired gag reflex); thus, securing of the airway and ventilation is occasionally necessary. A case of a 58‐year‐old female patient with depression who demonstrated a very high BAC of 8.68 gm/L (0.868%) following ingestion of large amounts of alcohol with suicidal intent is presented. Intubation and ventilation were life‐saving, and the patient did not develop any physical or consequential damage. As the patient had not regularly used alcohol or any other psychotropic agent, tolerance could be ruled out. This case emphasizes the necessity of rapid securing of the airway in patients with alcohol intoxication and respiratory depression and, furthermore, illustrates the large interindividual differences regarding ethanol susceptibility.