Two fatal intoxication cases with imidacloprid: LC/MS analysis

Imidacloprid [1-(6-chloro-3pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine] is a new and potent nitromethylene insecticide with high insecticidal activity at very low application rates. It is the first highly effective insecticide that, like nicotine, acts on the nervous system, causing blockage of postsynaptic nicotinergic acetylcholine receptors. Two fatal cases with this insecticide in two male individuals, of 33 and 66 years old, are presented. An LC/MS with electrospray method for measuring imidacloprid and its metabolites in post-mortem samples is described. In the chromatographic separation, a reverse-phase column XTerra MS C18 (2.1mm i.d.x 150 mm, 5 microm) was used and the mobile phase composed with acetonitrile and 0.1% formic acid (15:85), at a 0.25 mL/min flow rate. Samples were prepared with a liquid-liquid extraction procedure with dichloromethane. Calibration curves for imidacloprid in blood and urine samples were linear from 0.2 to 15 microg/mL. The mean recovery was 86% with a coefficient of variation of +/-5.9%. The detection limit was 0.002 microg/mL. Quantitative results were obtained for all post-mortem matrices available of the two fatal cases: blood, urine, stomach contents, lung, liver and kidney. The imidacloprid blood concentrations found in two-cases were 12.5 and 2.05 microg/mL. The authors validated a method to detect and quantify imidacloprid in post-mortem samples, and to our knowledge for the first time a post-mortem tissue distribution was performed on various samples for this insecticide.     

Suicide by hara-kiri: a series of four cases.

The authors describe four cases of suicide by hara-kiri. This very painful form of suicide consists of self-inflicting a wound in the abdomen using a sharp instrument. It was first reported in 988 A.D. in the East but has now become rare in both the East and West. These four cases occurred over a 40-year period in the Trieste and Bari medicolegal area. In two of our cases the victims were afflicted with mental illness, whereas the other two suffered from depression. In cases of death by hara-kiri, it is important to establish a differential diagnosis between suicide and homicide; the presence of trial wounds (inflicted by the victim as a form of practice to overcome any hesitation before stabbing the abdomen with the cutting weapon) can prove very helpful.     

Report of a fatal, acute tripelennamine intoxication.

A death resulting from tripelennamine overdose in a 19-year-old male Caucasian is reported. The patient died 7 h after ingesting approximately twenty 50-mg tripelennamine tablets. A concentration of 1.0 mg/100 ml was found in the blood. All tissue concentrations were measured by ultraviolet spectroscopy and verified by gas-liquid chromatography. Significant findings included pulmonary edema and multiple small petechial hemorrhages in the soft tissue of the scalp.     

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).     

美沙酮中毒死亡1例报告

美沙酮属于二苯甲烷类化合物,是人工合成的强效阿片受体激动剂.由于耐受性、成瘾性发生慢,症状轻,为临床上用于治疗阿片类药物依赖的有效药物(美沙酮维持疗法治疗项目Me thadone Maintenance Treatment Program,MMTP).随着MMTP项目的开展,陆续有美沙酮中毒的案例报道.本文报道一例误用美沙酮中毒死亡案例.     

Blood cyanide determination in two cases of fatal intoxication: comparison between headspace gas chromatography and a spectrophotometric method

Blood samples of two cases were analyzed preliminarily by a classical spectrophotometric method (VIS) and by an automated headspace gas chromatographic method with nitrogen-phosphorus detector (HS-GC/NPD). In the former, hydrogen cyanide (HCN) was quantitatively determined by measuring the absorbance of chromophores forming as a result of interaction with chloramine T. In the automated HS-GC/NPD method, blood was placed in a headspace vial, internal standard (acetonitrile) and acetic acid were then added. This resulted in cyanide being liberated as HCN. The spectrophotometric (VIS) and HS-GC/NPD methods were validated on postmortem blood samples fortified with potassium cyanide in the ranges 0.5-10 and 0.05-5 mug/mL, respectively. Detection limits were 0.2 mug/mL for VIS and 0.05 mug/mL for HS-GC/NPD. This work shows that results obtained by means of the two procedures were insignificantly different and that they compared favorably. They are suitable for rapid diagnosis of cyanide in postmortem cases.     

美沙酮中毒死亡1例报告

美沙酮属于二苯甲烷类化合物 ,是人工合成的强效阿片受体激动剂。由于耐受性、成瘾性发生慢 ,症状轻 ,为临床上用于治疗阿片类药物依赖的有效药物 (美沙酮维持疗法治疗项目ＭｅｔｈａｄｏｎｅＭａｉｎｔｅｎａｎｃｅＴｒｅａｔｍｅｎｔＰｒｏｇｒａｍ ,ＭＭＴＰ)。随着ＭＭＴＰ项目的开展 ,陆续有美沙酮中毒的案例报道。本文报道一例误用美沙酮中毒死亡案例。案例资料某男 ,2 7岁 ,口服麻黄素成瘾 15年 2月 ,平均每日一次 ,每次 13片 (15ｍｇ/片 ) ,曾有 2次不成功的戒毒历史。有长期大量饮酒史 ,最多一次可饮 75 0ｍｌ白酒。本次系因自觉躯…     

Dispensing error causing fatal chlorpropamide intoxication in a nondiabetic

A 38-year-old nondiabetic female developed fatal hypoglycemia when chlorpropamide (Diabinese) was accidentally substituted for acetaminophen (Tylenol) with codeine no. 3 in a pharmacy dispensing error. When found, the patient's serum glucose was less than 20 mg/dL. The serum chlorpropamide level on hospital admission was 124 micrograms/mL. The possibility of dispensing error should be considered whenever unexpected drug effects are encountered. In cases of suspected drug overdose, labels and contents of medicine vials found at the scene should be checked for discrepancy.     

Bupropion and alcohol fatal intoxication: case report.

A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l.     

A case of fatal intoxication from metformin

A case of fatal intoxication from metformin is presented. The decedent was an obese 58-year-old-woman with type II diabetes, in whom severe lactic acidosis secondary to metformin accumulation was precipitated by acute renal failure. She had been on metformin 500 mg twice a day. Postmortem blood was deproteinated with acetonitrile, washed with dichloromethane, and the resulting supernatant injected into high-performance liquid chromatography system. Separation was performed on a analytical 125 x 4 mm i.d. RP-8 column. The wavelength was set at 235 nm. The mobile phase was acetonitrile (40%), sodium lauryl sulfate, and sodium dihydrogen phosphate adjusted to pH 5.1 (60%) at a flow rate of 1.0 mL/min. The concentration of metformin in postmortem blood was 77.3 microg/mL. The qualitative result was also confirmed by LC/APCI/MS/MS analysis.     

An unusual form of fatal ethanol intoxication

Forensic pathologists are very familiar with deaths due to ethanol intoxication. The overwhelming majority of these deaths are a result of the oral ingestion of ethanol. We report an unusual case of an individual who expired in his secured residence after self administration of a wine enema. Toxicology showed an ethanol concentration of 0.40 g/dL in the blood and 0.41 g/dL in the vitreous fluid. Scene investigation was of paramount importance in determining the unusual method by which the decedent absorbed the alcoholic beverage.     

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.     

Distribution of dimethoate in the body after a fatal organophosphate intoxication

Many organophosphate pesticides (OPs) such as dimethoate are used to eradicate household pests, and those occurring in agriculture and forestry sectors. Combinations of two or more different insecticides have been manufactured to increase their effectiveness. A case of death is presented as suspected organophosphates intoxication. Autopsy was unremarkable except for grayish fluid in the stomach, with garlicky odor. A systematic toxicological analysis on post-mortem specimens revealed high concentrations of dimethoate in blood 38 microg/mL, urine 0.47 microg/mL, brain 2.2 microg/g, myocardial muscle 7.6 microg/g, liver 4.6 microg/g, lung 7.6 microg/g, skeletal muscle 21 microg/g, kidney 55 microg/g and gall bladder 31 microg/g. Blood alcohol was 2.85 g/L, cyclohexanone and cyclohexanol were also detected in the blood but not quantified. The cause of death was determined as organophosphate intoxication.     

Identification of human remains by comparison of frontal sinus radiographs: a series of four cases.

The value for identification purposes of the radiographic frontal sinus outline, which is unique to each individual and remains constant throughout that individual's lifetime, is discussed. A general discussion of identification using frontal sinus X-rays is presented, along with four cases.     

Nutmeg (myristicin) poisoning--report on a fatal case and a series of cases recorded by a poison information centre

In literature, cases of nutmeg abuse have been described repeatedly, but only one fatal case of poisoning was reported [1]. In the present case, myristicin (4 microg/ml) was detected for the first time in the postmortal serum of a 55-year-old woman. Identification was achieved with the aid of UV-VIS spectroscopy and TLC; for quantification, HPLC was used. Because also flunitrazepam (0.072 microg/ml) was found, death had probably been due to the combined toxic effect of both substances. From 1996 to 1998, in a series of cases, seven poisonings with nutmeg were recorded by the Erfurt Poison Information Centre. Even where higher doses (20-80 g of powder) had been ingested, a life-threatening situation was never observed. In one of these cases, a myristicin blood level of 2 microg/ml was measured 8h after ingestion of two to three tablespoonful of nutmeg powder (approx. 14-21 g, or 280-420 mg/kg).     

Fatal intoxication by dextromethorphan: a report on two cases

A report is given of two young people who died after intake of dextromethorphan, one by suicide and the other for uncertain reasons. To our knowledge this is the first reported fatal intoxications with this drug.