Frank Musshoff

Forensic Toxicological Centre, Munich, Germany

Background: There is increasing evidence for oxytocin as a neurotransmitter in spinal nociceptive processes. Hypothalamic oxytocinergic neurons project to the spinal dorsal horn, where they activate GABA-ergic inhibitory interneurons. The present study tested whether the long-acting oxytocin-analogue carbetocin has anti-nociceptive effects in mult...

Background: A 22-year-old male with a known history of drug abuse presented to our department with prolonged agitated delirium, myocloni, tachycardia and subfebrile temperature after the deliberate ingestion of opium poppy tea (Papaver somniferum L.) together with the methaqualone analog SL-164 (5-chloro-3-(4-chloro-2-methylphenyl)-2-methyl-4(3H)-q...

One of the major challenges of testing drugs of abuse is the detection of highly diluted urine samples. The ingestion of a large amount of fluid can considerably reduce the concentration of substances, possibly resulting in inaccurate drug testing. For detection, determination of urinary creatinine is a widely established procedure. In this study,...

Hair is the matrix of choice in forensic toxicology when retrospective analysis is needed. Nonetheless, due to misalignment, different growth stages and segmentation lengths of 0.5–1 cm, resolution of time is limited. By segmental analysis of single hairs, most of these factors can be compensated and resolution of time is enhanced. A method for man...

Zusammenfassung. Abstract: Hintergrund: Direkte und indirekte Alkoholkonsummarker sind in forensischen und klinischen Kontexten wie riskantem oder schädlichem Trinken, Rückfall oder Abstinenz von Bedeutung. Hierbei können je nach Fragestellung einzelne oder auch eine Kombination von Markern hilfreich sein. Methode: Es wurde eine Literaturrech...

Driving under the influence of drugs (DUID) is a serious global problem and poses a public health risk. With new psychoactive substances (NPS) entering the illicit drug market several years ago, a significant number of highly potent and harmful drugs have easily become available and the use of these substances may impair a person’s ability to drive...

This retrospective report focuses on the diagnosis of the Paxillus syndrome, based on two fatal cases of haemolysis following the consumption of Paxillus involutus. These mushrooms are still consumed regularly, despite earlier reports of life-threatening autoimmune haemolytic anaemia. Such cases are nevertheless rare, and thus far no toxin could be...

5F-ADB is an indazole-based synthetic cannabinoid. In recent years, it has been detected in legal high products as well as in biological samples and is associated with serious adverse health, behavioral effects and even death. Due to the fast pace of the market of synthetic cannabinoids, data on such newly appearing substances are scarce. As pharma...

Most recently, the synthetic opioid U-47700 has emerged on the illicit drug market and is sold on the Internet as a “research chemical”. Its structure is closely related to the synthetic opioid AH-7921. U-47700 is a μ-opioid receptor agonist with a potency of approximately 7.5 times that of morphine. In this study, postmortem concentrations of U-47...

Highly diluted urine is among the most commonly observed factors affecting the validity of urine testing for drug abuse. A minimum creatinine concentration of 20 mg/dL urine has been proposed as a marker for dilution of a urine sample. This study investigates the effect of water consumption on creatinine concentration, as well as its effect on spec...

Since there are no characteristic morphological findings post mortem diagnosis of diabetes mellitus and identification of diabetic coma need to be confirmed by suitable biomarkers. The postmortem identification of preexisting hyperglycemia or diabetic coma can be difficult if the matrices for the determination of the established biomarkers are not...

Testing hair for cannabis use has increasingly been scrutinized due to exposure to second hand smoke or environmental contamination. Confirmation of drug use involving detection of metabolites such as 11‐nor‐9‐carboxy‐delta‐9‐tetrahydrocannabinol (THC‐COOH) and 11‐hydroxy‐delta‐9‐tetrahydrocannabinol (THC‐OH) having very rarely been considered. We...

Drugs which are commonly smoked or sniffed (e.g. cocaine), can contaminate hair through smoke or dust; therefore testing for metabolites, especially hydroxy metabolites, is highly recommended. The presence of hydroxy metabolites in street-cocaine (COC) has been discussed. To check if detection of hydroxy metabolites definitely proves ingestion, the...

Because of the lack of characteristic morphological findings post mortem diagnosis of diabetes mellitus and identification of diabetic coma can be complicated. 1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, competes with glucose for renal reabsorption. Therefore low serum concentrations of 1,5-AG, reflect hyperglycemic excursions over t...

Although hair is widely used to identify drug use, there is a risk of false positives due to environmental contamination; this especially applies to cocaine (COC). Several strategies such as detection of norcocaine (NCOC) or cocaethylene, metabolite concentration ratios or intricate washing procedures have been proposed to differentiate actual use...

In this study, two fatalities associated with the synthetic opioids AH-7921 and MT-45 are reported. Within the last few years, both compounds have emerged on the recreational drug market and are sold as “research chemicals” on the internet. In the first case, a 22-year-old woman was found dead in the bedroom of her apartment by two of her friends....

Discrimination between street heroin consumption and poppy seed ingestion represents a major toxicological challenge in daily routine work. Several difficulties associated with conventional street heroin markers originate from their versatile occurrence in various poppy seed products and medications, respectively, as well as to small windows of det...

The organic cation transporter OCT1 (SLC22A1) mediates uptake and metabolism of the active tramadol metabolite (+)O-desmethyltramadol in the liver. . In this study the influence of OCT1 genetic polymorphisms on pharmacokinetics and analgesic efficacy of tramadol in patients recovering from surgery was analyzed in addition to the CYP2D6 genotype. Po...

Toxikologie ist die Lehre von den Giften und Vergiftungen. Vergiftungen spielen unter verschiedensten rechtlichen Fragestellungen eine Rolle. Vergiftungsursachen aus kriminalistischer Sicht sind: Vorsätzliche Fremdbeibringung, absichtliche Selbstbeibringung und unabsichtliche Vergiftung durch fremde oder eigene Hand. Vergiftungen sind mit charakter...

Verkehrsmedizin fördert die Sicherheit des Menschen im Verkehr und versucht verkehrsbedingte Gesundheitsstörungen abzuwenden. Im Vordergrund stehen die Begutachtung der Fahreignung und Fahrtüchtigkeit (Fahrsicherheit). Die Ungeeignetheit kann durch körperliche oder geistige Mängel oder Mängel in charakterlicher Hinsicht gegeben sein. Fahreignung un...

Die Rechtsmedizin stellt sich heute als typisches Querschnittsfach dar, das medizinisches und naturwissenschaftliches Spezialwissen zur Beantwortung von Rechtsfragen beinhaltet. Im ärztlichen Bereich hat sich in den letzten Jahren neben den klassischen Aufgaben (Obduktion zur Klärung von Grundleiden und Todesursache, Traumatologie als Basis der Rek...

Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy) have become recreational drugs in German discotheques because of their euphoric and mood-brightening effects. However, their consumption involves considerable risks, which may even be lethal under certain circumstances. A 19-year-old man was taken to a university...

Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) have become recreational drugs in German discotheques because of their euphoric and mood-elevating effects. Their use involves considerable risks, however, which may even be lethal under certain circumstances. Retrospective analysis of the years 2009-2015 showed 1...

Levamisole is an anti-helminthic drug and gained forensic interest after it was found that it was used as a cocaine adulterant. A liquid chromatography-mass spectrometry (LC-MS) method for the determination of levamisole and its metabolite aminorex in human plasma is described. Selectivity is given; calibration curves were linear within a calibrati...

The imidazoline derivative xylometazoline, an alpha-2-adrenergic agonist, is used as non-prescription nasal preparation due to its vasoconstrictive and decongestive properties. Especially in children, an overdose can quickly cause severe central nervous system depression and cardiovascular adverse effects. In three 3-year-old boys (triplets) a xylo...

Laboratory investigations in forensic science involve the examination of a wide range of items and substances using the highest analytical standards in compliance with the requirements of ISO/IEC 17025, as interpreted for forensic science laboratories (ISO/IEC 1998, 2005). Today we have national guidelines for autopsy standards in many countries, a...

In ontwikkelde landen is diabetes een van de tien meest voorkomende doodsoorzaken. Het post mortem vaststellen van stoornissen in het glucosemetabolisme kan een lastige en onduidelijke zaak zijn vanwege het ontbreken van kenmerkende morfologische bevindingen. We presenteren literatuuronderzoek betreffende biochemische problemen in gevallen van ondu...

There is a need for quick and reliable methods for rapid screening of drug-influenced drivers on the roadside by police. Because the window of detection in oral fluid is more similar to blood than to urine, this matrix should therefore be appropriate for screening procedures. The performance of the Rapid STAT® (Mavand Solution GmbH, Mössingen, Germ...

The appearance of dangerous and insufficiently studied designer drugs has increased substantially within the last few years. Mixtures containing centrally active compounds are often declared as "bath salt", "incense", "plant food", "bong cleaners" and are marketed in head shops and on the Internet. As the majority of the ingredients of such product...

Fatty acid ethyl esters (FAEE), direct metabolites of ethanol, are suitable alcohol markers that can be detected in different tissues. The determination of FAEE in hair can help to evaluate social and excessive alcohol consumption. Due to the presence of FAEE in the hair of teetotalers, proving alcohol abstinence seems to be impossible. To verify t...

The Capuchin Catacombs of Palermo contain over 1800 preserved bodies: friars, priests and laypeople including men, women, and children. The bodies were accessible to family members who could visit the deceased and commemorate them through prayers. The "Sicily Mummy Project" analyzed hair samples from 38 mummies to determine the presence of ethyl gl...

Diabetic coma is the most severe form of hyperglycaemic metabolic disorders. The post-mortem diagnosis of this disorder of glucose metabolism can be difficult and vague due to a lack of characteristic morphological findings. Six death cases caused by diabetic coma are described with special focus on biochemical (and histological) findings. The poss...

A nurse administered the neuromuscular blocking agent succinylcholine (SUX) to at least one patient and gave first aid in the therapy of unexpected respiratory depression. SUX is regarded as an undetectable and thus perfect poison due to its short half-life and degradation to the endogenous compounds choline and succinic acid. However, SUX and espe...

The determination of human insulin or its synthetic analogues in post-mortem specimens represents a challenge for forensic toxicologists due to its proven instability in post-mortem blood. We present two cases of an insulin-induced hypoglycaemia. In the first case, ante-mortem material was available for the detection of an injection with human insu...

Die 83 Jahre alte Patientin wurde mit einer Schenkelhalsfraktur bei noch nicht bekanntem Adenokarzinom stationär behandelt und entwickelte im Verlauf der Behandlung ungewöhnliche Komplikationen. Durch Zufall wurde im Rahmen einer Koloskopie eine silbrige Flüssigkeit im Darm festgestellt. Nach dem laborchemischen Nachweis von Quecksilber erfolgte di...

Nach 7½-jähriger Lagerung in einem Erdgrab wurden forensisch-toxikologische Analysen an verschiedenen Proben vorgenommen, die bei einer Sektion des teilskelettierten Körpers gewonnen worden waren. Für Pipamperon und Haloperidol wurden in Restgeweben positive Befunde im Spurenbereich ermittelt; die Medikation mit beiden Arzneimittelwirkstoffen war b...

This article presents a case of suicide by intoxication with various pharmaceuticals, particularly anticonvulsants, combined with the fungicide captan. A cause of death could not be ascertained at autopsy. However, systematic toxicological analysis (STA) including a screening via solid-phase microextraction (SPME) and gas chromatography-mass spectr...

In a preliminary test, four single hairs of a drug abuser were analyzed for the presence of drugs by MALDI Fourier transform mass spectrometry (MALDI-FTMS). Washed hair strains were directly fixed on a sample plate using pressure stable, double-sided adhesive tape; α-cyano-4-hydroxycinnamic acid matrix was manually spotted onto the hair strains. FT...

A preliminary initial cloned enzyme donor immunoassay (CEDIA) was optimized for serum and urine drug testing with respect to the German per se limits for driving under the influence of drugs (serum) and lowered cut-offs in cases of driving licence re-granting (urine). The tests were performed on an Olympus AU 400 auto analyzer. Validation revealed...

Recreational use of synthetic cannabinoid receptor agonists-so-called "Spice" products-became very popular during the last few years. Several reports on clinical symptoms and poisonings were published. Unfortunately, most of these reports do not contain any analytical data on synthetic cannabinoids in body fluids, and no or only a limited number of...

Background: The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites a...

A 42-year old-man was found lying in his bed having seizures. Later he became unconscious and hypotonic developing mydriasis as well as rigidity. The body core temperature (rectal temperature) was above 42 °C. Blood pH was decreased during treatment, and his general condition deteriorated. The patient developed gasping respiration, ventricular fibr...

The antihelminthic drug Levamisole can enhance cocaine effects by conversion into the amphetamine-like drug aminorex. We describe an LC-MS method for the determination of levamisole and its metabolite aminorex in human urine. Selectivity is given, calibration curves were linear within the calibration range 2.5-250 ng/mL; limits of the method were L...

Numerous death cases due to suffocation in a toxic or oxygen deficient gas atmosphere have been described in the literature, but unfortunately especially cases involving inert gases like helium are often presented without detailed toxicological findings. Observations on two suicides are reported, one by helium and the other by argon inhalation.Duri...

Das Münchhausen-by-Proxy-Syndrom ist eine Form der Kindesmisshandlung. Täterin ist in der Regel die Mutter. Sie erzeugt bei ihrem Kind ein physisches oder psychisches Beschwerdebild. Das Kind wird dann immer wieder zur medizinischen Diagnostik und Therapie vorgestellt. Die Täterin leugnet den wahren Hintergrund der Symptome und zieht einen psychisc...

Succinylcholin (SUX) ist ein depolarisierendes Muskelrelaxans, das eine potenziell letale Atemlähmung auslöst. Aufgrund dieser Wirkung besitzt SUX forensische Relevanz, da es z. B. bei Körperverletzungs- und Tötungsdelikten Anwendung finden kann. Das Erkennen einer SUX-Intoxikation ist aufgrund oft nur subtiler Hinweise stark erschwert. Nichtsdesto...

Possible fatal complications of human insulin and its synthetic analogues like hypoglycemia require precise classification and quantitative determination of these drugs both for clinical purposes as well as for forensic toxicologists. A procedure was developed for the identification and quantification of human insulin and different long-acting as w...

The postmortem determination of hyperglycaemic coma is quite difficult because of the lack of morphological findings and the difficult interpretation of biochemical parameters. Methylglyoxal (MG) is a reactive oxoaldehyde, which is mainly derived from glycolysis. An electrospray ionisation liquid chromatography-tandem mass spectrometric procedure f...

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are commonly used alcohol markers for previous alcohol consumption. Nevertheless, the optimum EtG cutoff for urinary abstinence tests is still being discussed, and no cutoff has been recommended for EtS yet. The aim of this study was to verify cutoffs by investigating EtG and EtS concentrations (cEtG...

Postmortem diagnosis of diabetes and a diabetic coma can be difficult because of the lack of characteristic morphological findings. 1,5-Anhydroglucitol (1,5-AG), the 1-deoxy form of glucose, competes with glucose for reabsorption in the kidneys. Therefore, diabetics with a permanent hyperglycemia show significantly lower serum concentrations of 1,5...

Endurance exercise is known to promote sustained antinociceptive effects, and there is evidence that the reduction of pain perception mediated by exercise is driven by central opioidergic neurotransmission. To directly investigate the involved brain areas and the underlying neural mechanisms in humans, thermal heat-pain challenges were applied to 2...

To the Editor: Chloroquine (CQ) has been used for the treatment and prophylaxis of malaria since World War II. Ten years later, the administration of CQ and hydroxychloroquine (HCQ) was introduced for the longterm therapy of rheumatic diseases. Although no reliable statistical data are available, HCQ, which differs from CQ only in a hydroxyl grou...

There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected...

Ethyl glucuronide (EtG) analysis in hair is a suitable method for the retrospective determination of previous alcohol consumption. According to the German guidelines, EtG abstinence is improbable at c EtG > 7 pg/mg in the proximal 3 cm of scalp hair. The chromatography of the routinely used liquid chromatography-tandem mass spectrometry procedure w...

Scientific opinions differ whether the use of stimulants causes deterioration in driving skills. In 1857 of 8709 cases of driving under the influence of drugs, amphetamine-like drugs (amphetamine, methamphetamine, and methylendioxyamphetamine) were present either alone or together with other licit or illicit drugs. In 338 cases, amphetamines were t...

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are powerful markers for alcohol intake and abuse. Several analytical procedures for the quantification of EtG and EtG in serum and urine have been developed so far. Many of the published methods show limits of detections (LODs) or limits of quantifications (LOQs) for EtG in urine within the range of...

The muscle relaxant succinylcholine (SUX) evokes respiratory paralysis, and numerous cases of fatal SUX intoxication have been reported. Detection of SUX and its metabolite succinylmonocholine (SMC) is difficult, both due to their (bis-) quaternary structure and the extreme hydrolytic susceptibility of SUX, and data on degradation kinetics of SUX a...

Alcohol, drugs and medicines are recognized as leading factors for traffic accidents even with fatal outcome. Epidemiological data as well as basic information about alcohol, drugs and medicines are given, especially concerning driving effects. Finally, forensic-toxicological aspects concerning drug fatalities in transportation are discussed. Keyw...

Due to sensitive limits of detection of chromatographic methods and low limit values regarding the screening of drugs under the terms of impairment in safe driving (§ 24a StVG, Street Traffic Law in Germany), preliminary immunoassay (IA) tests should be able to detect also low concentrations of legal and illegal drugs in serum in forensic cases. Fa...

An influence of polymorphic cytochromes P450 (CYP) 2D6 genetic variants on antiemetic efficacy of ondansetron has been suggested. However, the role of CYP3A in ondansetron metabolism and efficacy has been unclear. In this study, we evaluated the hypothesis that genotype-dependent CYP2D6 and CYP3A activity selectively influences plasma concentration...

Intoxications with succinylcholine (SUX) lead to a potentially lethal respiratory paralysis, and forensic cases involving accidental or deliberate SUX-application have been reported. Detection of SUX as well as its metabolite succinylmonocholine (SMC) is difficult: both substances are analytically challenging, and the extremely short plasma half-li...

A preliminary initial enzyme-linked immunosorbent assay (LUCIO-Direct ELISA kit) and a preliminary DRI enzyme immunoassay were evaluated for drug detection in head hair with respect to lowered cutoff values recommended in Germany for the control of abstinence in cases of re-granting of drivers' licences. Following drug classes were included: cannab...

Vitreous humor (VH) is used for postmortem diagnosis of metabolic diseases and to clarify the postmortem interval. Because of its viscous nature, this fluid has to be liquefied prior to analysis; however variations in measured concentrations of the analytes are ascribed to different pre-analytical treatment methods with regard to. The aim of this s...

Chemical structures of the oral antidiabetic drugs and the internal standards usedin this method

Munchausen syndrome by proxy represents a variant of child abuse where in most cases the mother artificially fabricates physical or psychological symptoms in her child and repeatedly seeks medical help for frequently invasive assessment and treatment. The perpetrator denies any knowledge of the true origin of the symptoms. She experiences a psychol...

Quaternary ammonium compounds pose an analytical challenge. Mebezonium, a muscle-relaxing agent contained in veterinary euthanasia solution T61, was analyzed in body fluids, organs, and injection sites of a veterinarian by liquid chromatography-tandem mass spectrometry (LC-MS-MS) method. Additionally, embutramide and tetracaine, which are two other...

The detection of diabetic metabolism disorders raises problems in forensic practice and sudden death with a subsequent negative autopsy finding is a common problem. In the case of an unclear hypoglycaemia, the detection of oral antidiabetics allows the differentiation of hypoglycaemia due to oral antidiabetics from that due to other reasons (insuli...

An uncommon suicide by oral ingestion of potassium cyanide salts and contemporaneous inhalation of hydrogen cyanide is presented. A 48-year-old tradesman was found dead sitting in his car. A penetrating odor of bitter almonds was noticed when opening the doors. A camping stove and a cooking pot containing large amounts of dark blue crystals were fo...

Response to analgesics, anticancer pharmacotherapy and pharmacotherapy of other cancer related symptoms vary broadly between individuals. Age, disease, comorbidities, concomitant medication, organ function and patients' compliance may partly explain the differences. However, the focus of ongoing research has shifted towards genomic variants of phas...

Techniques of molecular biology have improved diagnostic sensitivity, accuracy and validity in forensic medicine very much, especially in the field of identification (paternity testing, stain analysis). Since more than 10 years these techniques - meanwhile well established in clinical disciplines - are used also for other applications in forensic m...

Unlabelled: Opposing effects of ondansetron and tramadol on the serotonin pathway have been suggested which possibly increase tramadol consumption and emesis when co-administered. In a randomized, double-blinded study, 179 patients received intravenous ondansetron, metoclopramide, or placebo for emesis prophylaxis. Analgesic regimen consisted of t...

Hair analysis is a powerful tool for retrospective drug analysis. By determining the minor ethanol metabolites ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) in hair, even a previous consumption of alcohol is detectable. However, previous studies showed a lack of correlation if both parameters are determined simultaneously. A further s...

Animal models of anxiety disorders emphasize the crucial role of locus ceruleus-noradrenergic (norepinephrine, NE) signaling, the basolateral amygdala (BLA) and their interactions in the expression of anxiety-like behavioral responses to stress. Despite clinical evidence for the efficacy of a β-noradrenergic receptor blockade with propranolol in th...

Urine testing for ethyl glucuronide (EtG) is used to spot recent alcohol intake and is utilized to document alcohol abstinence. However, other possible sources of ethanol existed when special beverages or foods were ingested. EtG concentration curves in urine were measured after the consumption of non-alcoholic beers, fruit juices, sauerkraut, and...

A liquid chromatographic-mass spectrometric assay with atmospheric pressure chemical ionization for quantification of ondansetron and its main metabolite 8-hydroxyondansetron in human plasma was presented. The enantiomeric separation was achieved on a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate). The validation data...

In continuation to part I, a literature review is presented concerning biochemical problems of forensic post mortem cases of unclear hyperglycaemia or hypoglycaemia. Clinical parameters for this purpose were recently reviewed. Particular attention was paid to the detection of diabetic ketoacidosis, of hyperosmolar coma, insulinoma, insulin-induced...

In 2009 cutoff values of assessment criteria to testify abstinence control in order to estimate driving ability were standardized in Germany. The cutoff values are lower than required in existing guidelines like SAMHSA and there is critical discussion about detection of low concentrations by using immunoassay, especially concerning amphetamines in...

Doubts concerning the applicability of succinylmonocholine (SMC) as a succinylcholine (SUX) marker have been issued. A comparative analysis of previously discussed tissues, i.e. brain, liver and kidney, was conducted to further elucidate this question by searching for diagnostically useful differences in analyte content in samples of SUX- versus no...

The Reiss-Engelhorn-Museen in Mannheim, Germany requested support from a toxicological laboratory in evaluating occupational exposures before a cleanup and renovation period in 2006. Samples of dust and dirt and scrapings of exhibits were collected from several locations. Following toxicologically relevant compounds could be identified by gas chrom...