曲马多在家兔体内的死后分布研究

目的研究曲马多在中毒家兔体内死后分布规律,为曲马多中毒检材采取提供实验依据。方法家兔经口给予10倍LD50曲马多,待家兔死亡后迅速解剖取样,气相色谱／质谱联用和气相色谱-FTD法测定其体液、脏器、大脑及右上肢和右下肢肌肉中曲马多的含量,比较其变化规律。结果血液和肝脏中曲马多的最低检出限分别为0．05μg/mL和0．05μg/g,提取回收率为97．60％±0．65％～103．10％±1．24％。曲马多在家兔体内的死后分布为：肾〉胃〉肝〉脾〉肺〉脑〉心〉上肢肌肉〉下肢肌肉〉〉体液（尿〉胆汁、心血〉玻璃体液）。结论大剂量曲马多中毒致死后在体内分布不均匀,组织中曲马多含量明显高于心血、胆汁等体液。     

Simple analysis of arylamide herbicides in serum using headspace-solid phase microextraction and GC/MS

A simple and sensitive method for analysis of four arylamide herbicides (butachlor, propanil, diphenamide and propyzamide) in serum was developed using a headspace–solid phase microextraction (SPME) and a gas chromatograph–mass spectrometer (GC–MS). A vial containing a serum sample and sodium chloride was heated at 90°C. The extraction fiber of the SPME was exposed for 45 min in the headspace of the vial. The compounds adsorbed on the fiber were desorbed by exposing the fiber in the injection port of the GC–MS. The calibration curves, using an internal standard method, demonstrated good linearity throughout the concentration range from 0.25 to 10.0 μg/ml. Propyzamide was used for an internal standard. The limit of detection was 0.10, 0.05, and 0.25 μg/ml for butachlor, diphenamide, and propanil, respectively. No interferences were found, and the time for analysis was 60 min for one sample. In addition, this proposed method was applied to a suicide case in which the patient ingested Kusanon A^®, a herbicide. Propanil, which was the main ingredient in the herbicide, was detected in the eight serum samples collected from the patient during the hospitalization at the concentration range from 26.7 to 1.1 μg/ml.     

Lethal mixed intoxication with propofol in a medical layman

The authors report on a drug fatality of a 21-year-old man with a propofol (2,6-di-isopropylphenol) dependency. Propofol was detected in tissues and body fluids using SPME-GC/MS methods. The postmortem concentrations of propofol were 364 ng/ml in urine, 71 ng/ml in heart blood and 79 ng/ml in femoral blood. The drug addict had only an autodidactic medical knowledge, but had inserted himself a permanent cannula for intravenous injection of propofol several times a day. The injection material was bought via online auctions from eBay. The case illustrates how job-related drug dependencies become indistinct due to the free access to information and goods via the Internet.     

Toxicological analysis after asphyxial suicide with helium and a plastic bag

A 23-year-old man was found on a raised hide in lying position, the head wrapped in a plastic bag connected with a helium gas cylinder by a polypropylene tube. The autopsy did not show any specific findings nor did the routine toxicological analysis reveal significant information regarding the cause of death (BAC 0.9 mg/g, diphenhydramine 0.81 μg/ml in heart serum). For the detection of helium in the lungs, gas samples from both lungs were collected by a method ensuring minimal dilution. Gas analyses were performed using a GC–MS with a split–splitless injector and a headspace syringe. As carrier gas the commonly used helium was replaced by nitrogen. Helium was found in clearly elevated concentrations in gas samples from both lungs. Therefore, suffocation by breathing helium enriched, and thus oxygen deficient atmosphere, can strongly be assumed as the cause of death.     

苯并二氮类药物及其主要代谢物的薄层色谱分析

目的建立饮料、血、尿中 11种常见苯并二氮类药物及尿中 7种主要代谢物的薄层色谱分析法(HPTLC)。方法分析物采用GDX10 1树脂进行固相萃取 ,乙醚作为洗脱溶剂。苯 :丙酮 (10∶6)等作为展开体系 ,改良碘化铋钾显色。结果所建方法绝对灵敏度 0 3～ 0 6μg,尿检出限 0 4～ 1 0 μg/ml、血检出限 0 6～ 1 0 μg/ml、饮料检出限 0 4～ 0 8μg/ml。结论HPTLC法简便、快速 ,适合作为常规毒物分析方法     

Interpretation of a 3,4-methylenedioxymethamphetamine (MDMA) blood level: discussion by means of a distribution study in two fatalities

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy" is a currently used or abused designer drug and fatalities are frequently encountered in forensic practice. However, the question remains open whether an MDMA blood level can be toxic or even potentially lethal. In order to provide insight in the interpretation of a detected MDMA concentration, the distribution of MDMA and its metabolite 3,4-methylenedioxyamphetamine (MDA) in various body fluids and tissues was studied and discussed in two different fatalities. Apart from peripheral blood samples (such as femoral and subclavian blood), various blood samples obtained centrally in the human body and several body fluids (such as vitreous humour) were examined. In addition, various tissues such as cardiac muscle, lungs, liver, kidneys, and brain lobes were analysed. In contrast to the peripheral blood levels, high MDMA and MDA levels were found in cardiac blood and the majority of the organs, except for the abdominal adipose tissue. The high concentrations observed in all lung lobes, the liver and stomach contents indicate that post-mortem redistribution of MDMA and MDA into cardiac blood can occur and, as a result, blood sampled centrally in the body should be avoided. Therefore, our data confirm that peripheral blood sampling remains "the golden standard". In addition, a distinct difference in peripheral blood MDMA concentrations in our two overdose cases was established (namely 0.271 and 13.508 microg/ml, respectively). Furthermore, our results suggest that, if a peripheral blood sample is not available and when putrefaction is not too pronounced, vitreous humour and iliopsoas muscle can be valuable specimens for toxicological analysis. Finally, referring to the various mechanisms of death following amphetamine intake, which can result in different survival times (e.g. cardiopulmonary complications versus hyperthermia), the anatomo-pathological findings and the toxicological results should be considered as a whole in arriving at a conclusion.     

Detection of methamphetamine in mouse femurs exposed to high temperature

Bone samples are valuable for examining the cause of death and circumstance leading up to death when body fluids are not available for forensic toxicological analysis. Examined were heat-induced changes in methamphetamine and amphetamine concentrations in femurs removed from methamphetamine-injected mice to determine if the burned bones could be used for toxicology testing. The femurs were heated at 100°C, 300°C, or 500°C for 10 or 30 min. The tissue structure of the heated femurs was preserved at 100°C for 30 min but was destructed at higher temperatures. Methamphetamine and amphetamine were detected in femurs heated at 100°C for 10 min, 100°C for 30 min, and 300°C for 10 min (with methamphetamine and amphetamine concentrations ranging from 0.36 to 35 μg/g and 0.54 to 47 μg/g, respectively). Methamphetamine and amphetamine were detectable when heated above their decomposition temperature as a result of limited heat transfer do to protection provide by the femoral muscle. Thus, the bone could be a useful analytical sample in cases of burn-related deaths, where it is difficult to collect body fluids.     

Testing for alpha-chloralose by headspace-GC/MS. A case report.

A case is presented involving an acute fatality resulting from self-administered alpha-chloralose, a rodenticide. A 18-year-old man was found dead at home, with several stains of vomit on the carpet. An empty box of three bags of 5 g 100% alpha-chloralose (Corbeaux nuisibles, Rh?ne Poulenc) was found near the body. The compound was identified and quantified by headspace gas chromatography coupled to mass spectrometry. Alpha-chloralose was converted by concentrated sulphuric acid into chloral, a volatile compound, that was, after chromatography on a HP5-MS capillary column, identified by the following ions, m/z 82, 111 and 148. Peripheral blood concentration was 175.7 mg/l. Alpha-chloralose was quantified in several tissues, indicating kidney sequestration. No other drugs, including ethanol, were detected.     

Components of paint thinner in body fluids clearly detected using the salting-out technique

For a more sensitive detection of paint thinner components in body fluids, we made use of a salting-out technique, with sodium chloride added to blood samples followed by gas chromatography, using the headspace method. The detection of ethyl acetate and isobutanol was considerably enhanced using these approaches.     

Methanol intoxication: distribution in postmortem tissues and fluids including vitreous humor

A 44-year-old man was found unconscious beneath an elevated rapid transit right-of-way. On admission to the emergency room, the patient was comatose in metabolic acidosis with high anion and osmolal gaps. The serum methanol was 583 mg/dL. The serum ethanol and ethylene glycol were negative. The patient was treated with ethanol, bicarbonate, and hemodialysis. He expired 40 h after admission. The postmortem methanol concentrations in body fluids were as follows: bile 175 mg/dL, vitreous humor 173 mg/dL, and blood 142 mg/dL. Urine was not available for analysis. Postmortem methanol concentrations in body tissues are given in decreasing order: brain 159 mg/100 g, kidney 130 mg/100 g, lung 127 mg/100 g, spleen 125 mg/100 g, skeletal muscle 112 mg/100 g, pancreas 109 mg/100 g, liver 107 mg/100 g, and heart 93 mg/100 g. The total amount of methanol in the gastric contents was 73 mg. Methanol determinations were performed on a Hewlett-Packard 5840A gas chromatograph with flame ionization detection using a glass column packed with 0.2% Carbowax 1500 on Carbopack C. The internal standard used was n-propyl alcohol.     

Tissue distribution of DDVP after fatal ingestion

Tissue distribution of dichlorvos (DDVP) was determined in a case of fatal ingestion using a rapid and simple gas chromatographic (GC) assay. Remarkable autopsy findings were congestion of the lung and kidneys and bleeding ulcer extending from the dorsum of the tongue to the upper pharynx. The serum cholinesterase activity was 2 IU/l, however, miosis was not observed. In the stomach, 250 ml of volatile fluid was found. Tissue distribution of DDVP was determined using a newly developed simple and rapid GC method. DDVP was found in the spleen and heart at higher concentrations (3340 and 815 μg/g, respectively), and also detected in the urine at the lowest level (4.5 μg/ml). The DDVP concentrations in blood, brain, lung, kidney and liver were 29, 9.7, 81, 80 and 20 μg/ml or g, respectively.     

Last performance with VIAGRA: post-mortem identification of sildenafil and its metabolites in biological specimens including hair sample

A 43-year-old man was found dead in a hotel room during a sexual relation with a colleague.He was treated both for cardiovascular disease and for erectile dysfunction with VIAGRA. A pillbox was found in the room with several tablets of verapamil (Isoptine), trimetazidine (Vastarel), yohimbine and bromazepam (Lexomil). A box of VIAGRA 25mg was found in his raincoat and two tablets were missing. His wife declared during the investigation that he was also treated by trinitrine. Autopsy revealed severe coronary artery sclerosis as well as signs of previous myocardial infarctions. Blood, urine, bile, gastric content and hair and representative tissues for histology were collected for toxicological analysis.Sildenafil and yohimbine were screened with liquid chromatography/mass spectrometry (LC/MS) and trinitrine with headspace injection (HS)/GC/MS. Verapamil and trimetazidine were identified and quantified with LC/diode array detection (DAD).Sildenafil was identified in blood, urine, bile and gastric content at 105, 246, 1206 and 754ng/ml, respectively. Hair concentration was 177pg/mg. The desmethyl metabolite was quantified in urine at 143ng/ml. Blood concentrations of verapamil and trimetazidine were measured at 659 and 2133ng/ml, respectively and were above therapeutic ranges. Trinitrine and yohimbine were not identified.These results confirm the absorption of sildenafil, verapamil and trimetazidine before the death and hair analysis indicates the chronic use of sildenafil.To the author's knowledge, this is the first report of a fatal sildenafil-verapamil association, probably by hypotension and cardiac dysrhythmia.     

Insect larvae used to detect cocaine poisoning in a decomposed body.

Insect larvae are often found on human remains long after disappearance of the usual toxicologic specimens. It is important for forensic pathologists and toxicologists to recognize the potential of this unique specimen when routine specimens are not available. Cocaine and benzoylecgonine was extracted from Calliphorid larvae found on a badly decomposed body of a man who had been missing 5 months and was also identified in the decomposing skeletal muscle. This toxicologic information combined with the autopsy findings and the circumstances of the death and disappearance was essential in the determination of cocaine poisoning as the cause of death.     

Postmortem formation of carbon monoxide

Since carbon monoxide (CO) production after death was suggested in a drowned body, CO and carboxyhemoglobin (HbCO) levels in blood and body cavity fluids of cadavers which were not exposed to fire and CO have been analyzed. CO released from the tissues was determined by gas chromatography and gas chromatography-mass spectrometry, and the total concentration of hemoglobin (Hb) was measured as cyanmethemoglobin (CNmHb). The HbCO level was calculated by the ratio of CO content and CO-binding capacity. CO levels (ml/100 g at STP) of the seven cases in which blood and body cavity fluids could be collected ranged from 0.13 to 0.87 in blood and 0.02 to 0.80 in body cavity fluids. HbCO levels in blood and body cavity fluids were from 0.3 to 6.0% and from 2.3 to 44.1%, respectively. In a typical case showing postmortem formation of CO, the CO levels in body cavity fluids were higher than that in blood. It is suggested that CO in a putrefied body is due to CO in blood prior to death and the CO formed by the decomposition of Hb, myoglobin and other substances during putrefaction. The significance of HbCO levels in body cavity fluids of cases with marked postmortem decomposition seems difficult to interpret without the value of HbCO in blood.     

Fatal suicidal injury of a radiocephalic arteriovenous fistula

A 59-year-old man was found dead in his living room. His body was covered with blood, but the only injury found was a 31-mm-long, transverse incision on the radial surface of the left forearm. Autopsy revealed that the injured vessel was an enlarged cephalic vein from a radiocephalic arteriovenous fistula (RC-AVF) that had been created 23 years before for hemodialysis. Cephalic vein injury is usually not fatal, but circumstantial evidence, autopsy, and histological findings suggested that hemorrhagic shock and death occurred within a short time after the self-inflicted incised wound. This may be explained by the blood flow rate in the RC-AVF, which can reach 12 ml/s; this is 25 times higher than the normal cephalic vein blood flow.     

LC-MS/MS analysis of pholedrine in a fatal intoxication case

Pholedrine (4'-hydroxymethamphetamine) is a cardiovascular agent exerting hypertensive and adrenergic effects. High doses may cause a drop in the peripheral circulation blood flow and increase blood pressure, heart rate and body temperature up to a state of central respiratory paralysis. A 15-year-old girl who suffered from heavy agitation and hallucinations was admitted to the intensive care unit in a comatose state. The clinical findings included a maximum heart rate of 170 bpm and a body temperature of 43.8 degrees C. Resuscitation measures were in vain and abandoned after approximately 2h. A toxicological emergency analysis using GC/MS revealed a considerable amount of pholedrine in blood and urine. A method for determining pholedrine in human body fluids utilizing high-performance liquid chromatography (HPLC)/tandem mass spectrometry (LC-MS/MS) with a turbo ion-spray source was developed, using D11-methamphetamine and D5-methylenedioxymethamphetamine as internal standards. Samples were prepared by SPE extraction using SPEC-C18AR/MP3((R)) columns, which yielded the best extraction recovery (67%). Chromatographic separation was achieved at pH 5 on an RP-18 stationary phase applying gradient elution from 50 to 70% of B (methanol/acetonitrile 3/1 (v/v), 0.02% acetic acid) in A (5mM ammonium acetate/acetonitrile 95/5 (v/v), 0.02% acetic acid). Supra-pure acetic acid was added to the post-column effluent with a flow rate of 0.2 microl/min to optimize ionization. Detection was carried out in the positive ionization, multiple reaction monitoring (MRM) mode. The chromatograms showed no interference from other substances. The limit of detection (LOD, S/N=3) of pholedrine was 0.8 ng/ml and its lower limit of quantification (LLOQ, S/N=10) 3ng/ml. The calibration curve was linear (r=0.999) in the range 1-100 ng/ml. Samples with higher concentrations were diluted to suit the working range. The intra-day R.S.D. between 5 and 80 ng/ml were 3.8-8.7% and the inter-day R.S.D. between 5 and 100 ng/ml were 6.7-10.7%. The pholedrine concentrations in blood and urine collected when the girl was still alive were 16.1 microg/ml (R.S.D. 10.5%) and 1120 microg/ml (R.S.D. 8%), respectively. In post-mortem samples, they were 23.0 microg/ml (R.S.D. 5.1%) in heart blood and 27.3 microg/g (R.S.D. 6.6%) in the liver.     

A fatal case of oral ingestion of methanol. Distribution in postmortem tissues and fluids including pericardial fluid and vitreous humor.

A 41-year-old man ingested orally a large quantity of methanol and was found dead at home. The presence of methanol in body fluids and tissues was determined by head-space gas chromatography. The blood ethanol and acetone were negative. Tissue distribution of methanol showed that the kidney presented the highest content of methanol (5.13 g/kg) followed by liver (4.18 g/kg), vitreous humor (3.96 g/l), heart (3.45 g/kg), urine (3.43 g/l), pericardial fluid (3.29 g/l), blood (2.84 g/l) and finally stomach content (2.21 g/l).     

Suicidal buflomedil intoxication

A suicidal intoxication of a young woman following an overdose of buflomedil is reported. She died in a hospital 17 hours after ingestion. In various body fluids the following buflomedil concentrations were determined: heart blood 24.5 microg/ml, liquor 21.3 microg/ml, bile 39.1 mg/ml and urine 138.6 mg/ml. Additionally the results of autopsy and histology are presented. Anemia of the internal organs was conspicuous; this finding is attributed to the vasodilating effect of buflomedil on the peripheral vessels.     

Determination of ethylene glycol tissue content after fatal oral poisoning and pathologic findings

A 23-year-old comatose man who had drunk an unknown amount of ethylene glycol was admitted to the hospital 5 hours after ingestion. The initial plasma ethylene glycol concentration was 116.2 mg/100 ml. A severe metabolic acidosis was present. Despite aggressive therapy with ethanol, hemodialysis, and intensive care support, the patient died 27 hours after poisoning. The plasma ethylene glycol concentration immediately before death was 35.9 mg/100 ml. Brain edema and acute renal tubular necrosis were evident at postmortem examination. Oxalate crystals were identified in both organs. Ethylene glycol content or concentration was determined in tissues and biologic fluids.