Thomas Daldrup

An analytical method for the rapid screening of organophosphate pesticides in human biological samples and foodstuffs

Gas chromatography with nitrogen/phosphorus sensitive detection (GC/PND) and electron impact mass spectrometry (GC/MS) with selected ion monitoring provides a simple, rapid and sensitive method for the determination of organophosphate pesticides (OPs). A selective single-step extraction of 23 different OPs in urine, blood, serum and food samples (baby food, soft drinks and instant soups suspected of contamination from a blackmailing scare) is described. The OPs were extracted with 1ml toluene (with and without addition of mevinphos as internal standard), using a 0.7ml aliquot of urine, blood or serum sample. Food samples (0.2g) were homogenised with water (0.5ml) before extraction. An amount of 1microl of the toluene phase (extraction supernatant) was analysed directly by GC/PND and GC/MS.The method was validated using spiked human serum. The OPs were mixed with serum containing 10mg/ml disodium ethane diamine tetraacetic acid disodium salt (EDTA disodium salt) and stored up to 10 days at 4 and -20 degrees C, respectively. The recovery rates of OPs in freshly spiked human plasma ranged between 50% (dimethoate) and 133% (dialifos). OPs in plasma proved to be stable at -20 degrees C. Their levels decreased only slightly after storage at 4 degrees C.

Sudden unexpected death under acute influence of cannabis.

The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis.

Suicides by starter's pistols and air guns

We report the case of a 25-year-old depressed woman who committed suicide with a starters pistol loaded with CS tear-gas ammunition. The propellant gases of the contact shot entered her chest through the left sixth intercostal space. Exsanguination was caused by perforations of the pericardium and apex of the heart. Autopsy did not reveal any metallic or other foreign bodies that might have originated from the propellant, the cartridge, or any bulletlike material. Her injuries were thus caused by the propellant alone. 0.5 mg L-1 of the CS degradation product cyanide was detected in the cardiac blood. We also report the case of a 54-year-old man, suffering from depressive psychosis, who committed suicide with an air rifle. The lead-pointed Diabolo bullet entered his brain through the right large wing of the sphenoid bone, traversed the right temporal brain pole, damaged the right middle cerebral artery and the right optic tract, and finally lodged in the left central ganglia. There was extensive basal subdural hemorrhage and tamponade of all cerebral ventricles. Death was attributed to cerebral failure. We furthermore list another 26 cases of suicide by rarely used weapons from 1947 to 1989.

Cyanide fatalities: case studies of four suicides and one homicide.

Deaths due to cyanide poisoning are relatively rare, largely owing to the restricted availability of cyanide. Nevertheless, the authors report five cases of cyanide fatalities occurring within a few months. Cyanide is one of the most rapidly acting poisons known and is still used for suicide and homicide. The discussion focuses on the circumstances, metabolic changes, pathophysiology, blood levels, diagnosis, and management of cyanide poisoning.

A rapid solid-phase extraction and HPLC/DAD procedure for the simultaneous determination and quantification of different benzodiazepines in serum, blood and post-mortem blood

SummaryA rapid and quantitative method for the determination of benzodiazepines using high-performance liquid chromatography (HPLC) with diode-array detection (DAD) is reported. The drugs were extracted from serum, blood or post-mortem blood using C18 extraction columns. Brotizolam was used as internal standard. Experiments with spiked serum/blood samples resulted in recoveries between 75% and 94% for all investigated benzodiazepines. Excellent linearity was obtained over the concentration range 5–1500 ng benzodiazepine/ml. The limit of detection was approximately 2 ng/ml. The detection of low therapeutic serum levels of highly potent benzodiazepines is also possible.ZusammenfassungEine schnelle Methode zur quantitativen Bestimmung von Benzodiazepinen mittels Hochleistungsflüssigkeitschromatographie (HPLC) mit Dioden-Array-Detektion (DAD) wird beschrieben. Die Substanzen werden aus Serum, Vollblut oder Leichenblut mit Hilfe von C18-Extraktionssäulen extrahiert. Brotizolam wird als interner Standard eingesetzt. Versuche mit aufgestockten Serum-/Blutproben führten für sämtliche untersuchten Benzodiazepine zu Wiederfindungsraten zwischen 75% und 94%. Eine ausgezeichnete Linearität wurde über den Konzentrationsbereich von 5–1500 ng Benzodiazepin/ml beobachtet. Die Nachweisgrenze lag für alle Substanzen bei annähernd 2 ng/ml. Auch für die niedrig dosierten Benzodiazepine ist die Erfassung der therapeutischen Konzentrationsbereiche gewährleistet.

Suicidal yew leave ingestion — Phloroglucindimethylether (3,5-dimethoxyphenol) as a marker for poisoning from Taxus baccata

SummaryIn a case of suicide in a depressive 19-year-old man with considerable ingestion of new leaves, resorption of yew ingredients could be demonstrated. The main substance could be identified as 3,5-dimethoxyphenol, the aglycone of taxicatine, which is a typical ingredient of yew leaves. 3,5-dimethoxyphenol was demonstrated in harvested yew leaves, stomach content and cardiac blood of the victim. Structure confirmation was achieved by means of HPLC, UV, GC-MS, IR and1H-NMR spectroscopy. None of the Taxus alkoids could be identified. The components detected by TLC have not yet been identified. The results demonstrate that 3,5-dimethoxyphenol can be used as a marker in cases of intoxication by yew ingredients.ZusammenfassungIm Rahmen der Untersuchung eines Suizides eines depressiv verstimmten 19jährigen Mannes mit einer großen Menge von Eibennadeln konnte die Resorption von Eibeninhaltsstoffen nachgewiesen werden. Als Hauptsubstanz fand sich 3,5-Dimethoxyphenol, das Aglykon des Taxicatins, ein eibentypischer Inhaltsstoff. Es wurde in geernteten Eibennadeln, im Magen und im Herzblut des Opfers nachgewiesen. Die definitive Strukturbestätigung des aufgefundenen 3,5-Dimethoxyphenols erfolgte durch HPLC, GC/MS, UV-, IR- and1H-NMR-Spektroskopie. Es konnten keine vom Taxin ableitbaren Alkaloide identifiziert werden. Dünnschichtchromatographisch nachgewiesene Inhaltsstoffe konnten nicht zu Alkaloidbruchstücken zugeordnet werden. Das nachgewiesene 3,5-Dimethoxyphenol kann als Leitsubstanz für den Nachweis von Intoxikationen mit Eibenbestandteilen herangezogen werden.

Fatal Accidental Enflurane Intoxication

Among reported cases of abuse of volatile anesthetics there is only one of enflurane intoxication. We report another fatal enflurane intoxication. A 21-year-old man found dead seemed to have experimented with enflurane. Three and one-half days after death high amounts of enflurane were detected in blood, brain, and subcutaneous fat. Gas chromatographic quantification revealed the following high enflurane concentrations: blood: 130 mg/l-1, brain: 350 mg/l-1, and subcutaneous fat: 100 mg/l-1. Histologic signs of drug-induced damage were lacking. No suicide intentions became known. It was concluded that the young man died of an accidental intoxication while abusing enflurane.

Gas chromatographic/mass spectrometric determination of lysergic acid diethylamide (LSD) in serum samples

A sensitive method for the detection and quantification of lysergic acid diethylamide (LSD) in serum samples is described. After liquid-liquid extraction the trimethylsilyl derivative of LSD is detected by gas chromatography-mass spectrometry. Experiments with spiked samples resulted in a recovery of 76%, the coefficient of variation was 9.3%. Excellent linearity was obtained over the range 0.1-10 ng ml-1. Additionally experiments demonstrating the light sensitivity of LSD are presented together with casuistics.

Salsolinol and Norsalsolinol in Human Urine Samples

The tetrahydroisoquinoline alkaloids salsolinol and norsalsolinol were found in human urine samples in concentrations ranging from 0.1 to 29.5 ng/ml. Great interindividual variation was found in urine levels of these alkaloids in a collection of chronic alcoholics and in a group of nonalcoholics. Thus, levels of the individual alkaloids are insufficient markers for distinguishing between alcoholics and nonalcoholics. However, by using the concentration ratio of norsalsolinol and salsolinol, the so-called dopamine-aldehyde adduct ratio (DAAR), significant differences between alcoholics (median 1.3) and nonalcoholics (median 0.6) were detected. This concentration ratio could serve as a marker for the processor state of the dopaminergic system.

Evaluation of a method for simultaneous quantification of codeine, dihydrocodeine, morphine, and 6-monoacetylmorphine in serum, blood, and postmortem blood

SummaryA solid-phase extraction and gas chromatographic-mass spectrometric method for the simultaneous determination of codeine, dihydrocodeine, morphine, and 6-monoacetylmorphine in serum, blood or postmortem blood is described. The extraction technique allows the determination of free or total morphine (morphine plus morphine glucuronide). Experiments with spiked blood samples resulted in recoveries of 96.4% ± 4.2% for codeine, 95.8% ± 5.1% for dihydrocodeine, 90.3% ± 7.8% for 6-monoacetylmorphine and 92.5% ± 8.1% for morphine. Excellent linearity was obtained over the range 1–1500 ng/mL. The detection limit for all analytes is less than 1 ng/mL.ZusammenfassungEine Festphasen-Extraktion und GC/MS-Methode zur gleichzeitigen Bestimmung von Codein, Dihydrocodein, Morphin und 6-Monoacetylmorphin in Serum, Blut und Leichenblut wird beschrieben. Die Extraktions-Technik ermöglicht die Bestimmung von freiem und Gesamtmorphin (Morphin plus Morphinglucuronid). Versuche mit aufgestockten Blutproben führten zu Wiederfindungsraten von 96.4% ±4.2% für Codein, 95.8% ±5.1% für Dihydrocodein, 90.3% ±7.8% für 6-Monoacetylmorphin und 92.5% ±8.1% für Morphin. Linearität wurde über den Konzentrationsbereich von 1–1500 ng/mL erhalten. Die Nachweisgrenzen liegen für alle Substanzen unter 1 ng/mL.