Cornelius Hess

Reference Institute for Bioanalytics

Analysis of new psychoactive substances (NPS) still pose a challenge for many institutions due to the number of available substances and the constantly changing drug market. Both new and well-known substances keep appearing and disappearing on the market, making it hard to adapt analytical methods in a timely manner. In this study we developed a qu...

Forensic toxicologists are frequently required to predict the time of last cannabis consumption. Several studies suggested the utility of minor cannabinoids as indicators of recent cannabis use. Because several factors influence blood cannabinoid concentrations, the interpretation of serum cannabinoid concentrations remains challenging. To assess t...

Gamma hydroxybutyrate (GHB) is a central nervous system depressant that is an approved drug for the treatment of narcolepsy with cataplexy and other syndromes. Due to its dose dependent stimulating, relaxing or sedative effects, illicit abuses include recreational use by young people and cases of drug-facilitated crime (DFC). Since GHB is also prod...

Amphetamine (‘speed’), methamphetamine (‘crystal meth’) and 3,4‐methylenedioxy‐N‐methylamphetamine (MDMA, ‘ecstasy’) represent the most frequently abused amphetamine‐type stimulants (ATS). Differences in pharmacological potency and metabolism have been shown for the enantiomers of all three stimulants. Legal consequences in cases of drug possession...

In crimes facilitated by γ‐hydroxybutyric acid (GHB) administration, the frequent occurrence of anterograde amnesia of the victims as well as the short detection window and variations of endogenous GHB concentrations complicate obtaining analytical proof of GHB administration. Because elevated endogenous organic acid concentrations have been found...

Increasing prescription numbers of cannabis-based medicines raise the question of whether uptake of these medicines can be distinguished from recreational cannabis use. In this pilot study, serum cannabinoid profiles after use of cannabis-based medicines were investigated, in order to identify potential distinguishing markers. Serum samples after u...

GHB related acids (3,4-dihydroxy butyric acid, 2,4-dihydroxy butyric acid and glycolic acid) are produced through oxidative GHB metabolism. These analytes could be potential biomarkers to ensure the diagnosis of a GHB intoxication and even prolong the detection window. Within this study, forensic routine cases were measured to consider the potentia...

The interpretation of postmortem γ-hydroxybutyric acid (GHB) concentrations is challenging due to endogenous existence and postmortem GHB-production in body tissues and fluids. As an additional complication, formation of GHB was also described in stored postmortem samples. We examined cardiac blood, femoral blood, vitreous humor, cerebrospinal flui...

Analysis of synthetic cannabinoids still pose a challenge for many institutions due to the number of available substances and the constantly changing drug market. Both new and well-known substances keep appearing and disappearing on the market, making it hard to adapt analytical methods in a timely manner. In this study, we developed a qualitative...

The potential therapeutic effects of various phytocannabinoids and the availability of multiple cannabis-based medicines make it desirable to have an analytical method that simultaneously quantifies a wide range of cannabinoids in blood, beyond delta-9-tetrahydrocannabinol and its metabolites. A liquid chromatography tandem mass spectrometry (LC-MS...

Objectives In a previous investigation we searched for the occurrence of palmitic acid ester compounds of delta9-tetrahydrocannabinol (THC) and its primary metabolite 11-hydroxy-delta9-THC (11-OH-THC) in human body fluids and tissues (THC palmitic acid monoester [THC-Pal] and 11-OH-THC palmitic acid diester [11-OH-THC-DiPal]). As those esters could...

As the frequency of cannabis-based therapy increases, the ability to distinguish intake of cannabis-based medicines from recreational cannabis use becomes desirable. Minor cannabinoids have been suggested to indicate recreational cannabis use in biological matrices but are unreliable when presumably also present in directly plantderived medicines....

Misuse of pregabalin and its forensic relevance is steadily increasing. Aim of this study was to evaluate the usability of the commercially available ARKTM pregabalin II assay (ARK Diagnostics), for serum analysis of forensic samples. Overall 156 samples were tested both by the immunoassay and a validated liquid chromatographic tandem mass spectrom...

Post mortem gamma hydroxy butyric acid (GHB) concentrations should be interpreted with caution since GHB concentrations can increase after death. Post mortem concentrations after the intake of GHB ante mortem do overlap with concentration ranges in cases without known exposure to GHB and make an interpretation challenging. GHB is known to undergo i...

Over the last two decades, misuse of 4-fluoroamphetamine (4-FA) became an emerging issue in many European countries. Stimulating effects last for 4-6 hours and can impact psychomotor performance. The metabolism of amphetamine-type stimulants is stereoselective and quantification of (R)- and (S)-enantiomers has been suggested for assessing time of u...

5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death. Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and fiv...

Gamma hydroxybutyric acid (GHB) is known as a sedative drug used in Drug Facilitated Crimes. Its detection window is very short. GHB undergoes intensive phase I metabolism to organic acids (glycolic acid, succinic acid, dihydroxy butyric acids). These could be potential analytical targets to broaden the detection window. The aim of the present stud...

Aphrodisiacs, libido or erection-enhancing supplements are widely available on the internet. The beneficial effects are controversial. Forensic toxicologists should be aware of the potential toxicities of these products because they could be given in cases of drug-facilitated sexual assault. This article presents a case report in which the defendan...

To assess the informative value of determining (minor) cannabinoids in plasma of cannabis users, detection rates of 14 cannabinoids (next to Δ⁹ -THC and THC-COOH) were determined. 11-OH-THC, THCA, CBC, CBN, and CBD were the most frequent detectable cannabinoids. The dependency of cannabinoid detectability on the plasma Δ⁹ -THC concentration was exa...

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...

We report a fatal g-hydroxybutyric acid (GHB) intoxication of a forty-year old man. According to an acquaintances’ statement, the deceased had drunk a beverage containing GHB approximately five hours before he was found. Postmortem GHB concentrations were determined using gas chromatography coupled to single quadrupole mass spectrometry after simpl...

The differentiation between single methamphetamine consumption and co-consumption with amphetamine is difficult, however possible by enantioselective analysis due to different preferred synthesis pathways of both substances. We quantified (R)-(−) and (S)-(+)-enantiomers of methamphetamine and amphetamine by a fast liquid chromatographic tandem-mass...

Cannabidiol (CBD) is a non‐psychoactive cannabinoid, which is of growing medical interest. Previous studies on the metabolism of CBD showed mainly the formation of hydroxylated or oxidized derivatives, of carboxylic acids or modifications of the aliphatic side chain. Using incubation of CBD with hepatic microsomes of mice, the formation of carbon m...

Fatty acid conjugates of hydroxy-metabolites of tetrahydrocannabinol (THC) or cannabinol have already been reported as metabolites in rats. In the herein presented investigation, palmitic acid esters of THC and its primary metabolite 11-hydroxy-delta9-tetrahydrocannabinol (11-OH-THC) were synthesized using esterification with palmitic acid chloride...

It has been estimated that 15% up to one third of cases of deaths due to diabetic ketoacidosis occur in individuals with so far unknown diabetes. Moreover, cardiac arrhythmias that occur during nocturnal hypoglycaemia include bradycardia and ectopics that may provoke lethal arrhythmias. As postmortem capillary glucose concentrations have no diagnos...

Methamphetamine can be synthesized either enantiopure or in its racemic form. We separated (R)- and (S)-enantiomers of methamphetamine and amphetamine by a fast LC-MS/MS-method using a Lux® 3μm AMP 150×3.0mm analytical column after simple protein precipitation with methanol. Sufficient resolution could be achieved. Method validation for qualitative...

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...

Purpose: In the present study we characterized a series of synthetic cannabinoids containing various heterocyclic scaffolds that had been identified as constituents of "Spice", a preparation sold on the illicit drug market. All compounds were further investigated as potential ligands of the orphan receptors GPR18 and GPR55 that interact with some...

Background: Synthetic cannabinoids are the largest group of new psychoactive substances monitored by the European Monitoring Center of Drugs and Drug Addiction. The rapid proliferation of novel analogs makes the detection of these new derivatives challenging and has initiated considerable interest in the development of so-called "untargeted" scree...

Due to a lack of reference values for blood concentration of metformin in the literature, the forensic evaluation of metformin findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested metformin amounts are often vague. Furthermore, post mortem evaluation o...

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...

We describe a case in which a 35 year old man injected himself a lethal dose of the aminosteroid non-depolarizing muscle relaxant rocuronium. He had stolen the syringes containing rocuronium (and other substances) from a hospital. Rocuronium was quantified in various matrices post mortem using high performance liquid chromatography coupled to tripl...

PurposePropofol is the most preferred drug for general anesthesia as well as for analgosedation. However, the rate of abuse cases has increased in the past decade. Hair analysis is considered as the method of choice to determine chronic drug use, and propofol and propofol glucuronide have already been used to confirm previous propofol administratio...

The requirement for correct evaluation of forensic toxicological results in daily routine work and scientific studies is reliable analytical data based on validated methods. Validation of a method gives the analyst tools to estimate the efficacy and reliability of the analytical method. Without validation, data might be contested in court and lead...

Due to a lack of reference blood concentrations in the literature, the forensic evaluation of prothipendyl findings in blood samples is difficult. Interpretations with regard to the assessment of blood concentrations as well as an estimation of the ingested prothipendyl amounts were often vague. To describe a concentration range in clinical samples...

Gamma-hydroxybutyric acid (GHB) acts as an agonist of the GABAB receptor, where GHB induces a depressant effect in the central nervous system. Besides its therapeutic application, GHB is also used as a date rape drug. However, the detection of GHB ingestion proves to be difficult due to its narrow detection window. The aim of this pilot study was t...

Besides its clinical application, the anaesthetic agent propofol is being increasingly misused, mostly by healthcare professionals, and its abuse potential gained worldwide attention after the tragic death of Michael Jackson in 2009. Due to the short duration of its narcotic effects, propofol abuse is especially easy to hide compared with the use o...

Recently, phase-II-metabolites of γ-hydroxybutyric acid (GHB), namely GHB-β-O-glucuronide and GHB-4-sulfate, were implemented in the scope of drug testing methods The clearance of GHB from the circulation is extremely fast due to its incorporation into the metabolic pathway of the citrate cycle. The elimination half-life of GHB from blood was repor...

Confirmation or exclusion of recent heroin consumption is still one of the major challenges for forensic and clinical toxicologists. A great variety of biomarkers is available for heroin abuse confirmation, including various opium alkaloids (e.g. morphine, codeine), street heroin impurities (e.g. 6-acetylcodeine (6-AC), noscapine, papaverine) as we...

The number of new psychoactive substances (NPS) that have emerged on the European market has been rapidly growing in the last years, with a particularly high number of new compounds from the group of synthetic cannabinoid receptor agonists. There have been various political efforts to control the trade and the use of NPS worldwide. In Germany, the...

Metabolism of the tricyclic azaphenothiazine neuroleptic drug prothipendyl was investigated with in vitro studies using human liver microsomes but also specific isoforms of cytochrome P450 (CYP) enzymes. Identification and analysis of metabolites was done by liquid chromatography (LC) coupled with quadrupole time of flight mass spectrometry (LC-QTO...

Gamma-hydroxybutyric acid (GHB) can be used as a knock-out drug in drug facilitated crime (DFC). Due to its rapid metabolism and resulting narrow detection window, uncovering GHB use in DFC still constitutes a problem. In this experiment we determined the GHB and GHB-β-O-glucuronide (GHB-Gluc) concentrations in hair samples after single and chronic...

Separation and identification of positional isomers is an important issue in forensic toxicology, particularly in the context of new psychoactive substances (NPS). Despite the structural similarity, positional isomers often show different pharmacological properties and thus can exhibit dramatic differences with respect to their toxicity. Additional...

A male driver was checked during a traffic stop. A blood sample was collected 35 minutes later and contained 7.3 ng/mL THC, 3.5 ng/mL 11-hydroxy-THC and 44.6 ng/mL 11-nor-9-carboxy-THC. The subject claimed to have used two commercially produced products topically that contained 1.7 ng and 102 ng THC per mg, respectively. In an experiment, three vol...

Because of its small detection window, uncovering drug-facilitated crime after gamma-hydroxybutyric acid (GHB) intake remains a problem. The aim of this experiment was to determine endogenous concentrations of GHB and GHB-O-β-glucuronide (GHB-Gluc) in plasma and urine samples and to compare them with concentrations after GHB intake in humans. Plasm...

Background: Propofol (2,6-diisopropylphenol) is a water-insoluble, intravenous anesthetic that is widely used for the induction and maintenance of anesthesia as well as for endoscopic and pediatric sedation. After admission, propofol undergoes extensive hepatic and extrahepatic metabolism, including direct conjugation to propofol glucuronide and h...

Analysis of the anesthetic agent propofol in biological samples by LC-MS/MS is a great challenge due to weak fragmentation and poor ionization efficacy of propofol resulting in weak signal intensities. Improvements of the ionization and fragmentation efficacy can be achieved by conversion of propofol to its dimethylimidazolesulfonyl (DMIS) derivati...

Information about stability of synthetic cannabinoids is important to give recommendations for storage conditions in cases in which use of synthetic cannabinoids is suspected. In this study freeze and thaw stability (3 cycles at -20 °C at 1.5 ng/ml) and long term stability at room temperature, 4 °C and -20 °C (until 150 days) were tested by a valid...

Gamma-hydroxybutyric acid (GHB) is used as a so-called knock-out drug in drug-facilitated sexual assault. Due to GHB’s short detection window in blood and urine, crime verification remains problematic in many cases. Phase II metabolites can enhance the detectability and prolong the detection window of some lower-molecular-mass molecules, as exempli...

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...

In a study on alcoholics, diabetics, cases of hypothermia, combinations of alcoholism, diabetes and hypothermia as well as 55 controls, ketone body measurements were performed in femoral vein blood, heart blood, vitreous humor, cerebrospinal fluid and urine. Histological investigations were carried out on the kidneys of the deceased. In addition to...

Pancuronium(bromide) is used because of its relaxing effect on striated muscles and usually requires artificial respiration. A 52-year-old woman suffered from long-standing "generalized dystonia", which had become resistant to conventional therapy. Therefore, an anesthetist established a permanent medication scheme with pancuronium using a PCA pump...

The Internet is flooded with steadily changing synthetic cannabinoids in `Spice` products. In routine forensic work, it is difficult to keep the analytical methods for the detection of these analytes up to date. We describe a liquid chromatography-tandem mass spectrometry method after liquid-liquid extraction for the detection of 93 synthetic canna...

In recent years, many synthetic cannabinoid (CB) receptor agonists have appeared on the market as constituents of herbal incense mixtures known as “spice”. Contrary to the declared use, they are perorally consumed as a replacement for marijuana to get “high”. In many cases, detailed information on the physicochemical and pharmacological properties...

In most cases, bodily harm results from the use of sharp objects or blunt force. This paper deals with a 42-year-old pharmacist who was known to the police and the courts because of several previous convictions for bodily injury. The man had visited a pub just before it closed and was therefore not served any drinks. He got angry about this and ret...

Fusobacteria belong to the normal population of the pharyngeal mucosa as well as the mucosa of the upper airways and the gastrointestinal tract. Infections are comparatively rare. The most common causative organism is Fusobacterium necrophorum. A well-known infection caused by this germ is Lemierre's syndrome. In the presented case, a 19-year-old m...

Diabetes mellitus is one of the most frequent chronic diseases worldwide. Of special clinical and forensic interest is the development of hypoglycemia, which can occur either spontaneously or after administration of insulin and oral antidiabetics. Not only hypoglycemia is of special forensic interest but also the so-called hypoglycemia unawareness...

New psychoactive drugs, so-called legal highs, have gained more and more popularity during the last years. One of the most important groups of these legal high substances are the synthetic phenethylamines that share a common phenethylamine moiety. Based on certain structural characteristics, these synthetic phenethylamines can be divided into furth...

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...

Alcoholic ketoacidosis is a medical emergency, which is characterized at first by an elevated level of ketone bodies. The production of these ketone bodies is accompanied by an equimolar quantity of hydrogen ions and thus causes acidosis, which cannot be detected post-mortem due to anaerobic glycolysis, whereas the three ketone bodies beta-hydroxyb...

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...

Diabetes mellitus ist eine weltweit auftretende chronische Erkrankung. Von ausgeprägtem klinischen und auch forensischen Interesse ist die Entwicklung einer Hypoglykämie, die sowohl spontan als auch infolge der Applikation von Insulin/Insulinanaloga bzw. oraler Antidiabetika auftreten kann. Hypoglykämien besitzen erhebliche verkehrsmedizinische Rel...

Bei „legal highs“ handelt es sich um synthetische Verbindungen mit psychoaktiven Wirkungen, die sich in Bezug auf Struktur und Wirkungsweise oft nur geringfügig von den bekannten illegalen Drogen unterscheiden. Neben der Strukturklasse der Phenethylamine gehören verschiedene Tryptamin- und Piperazinderivate sowie synthetische Cannabinoide zu diesen...

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...

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...

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...

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...

Methylglyoxal (MG), a highly reactive α-dicarbonyl metabolite of glucose degradation pathways, protein and fatty acid metabolism, plays an important role in the pathogenesis of diabetic complications. Hyperglycemia triggers enhanced production of MG and increased generation of advanced glycation endproducts (AGEs). In non-enzymatic reactions, MG re...

Measurement of GLUT4 translocation with and without insulin stimulus. (A) Change of fluorescence intensity in anti-c-myc(FITC) stained L6 cells with and without insulin stimulus. (N = 5, n = 2). **p<0.01 vs. untreated. Means ± SEM. (B) Representative histograms of fluorescence changes in anti-c-myc(FITC) stained L6 cells with and without insulin st...

Analysis of GLO1 Expression. (A) Representative western blot analysis performed with anti-GLO1 (Untr. = untreated cells, Ctr. = scrambled siRNA, A-C = three different GLO1 siRNAs) (B) Western Blot analysis for GLO1 of L6 cells transfected with three different GLO1 siRNA (following 72 h siRNA transfection). (N = 3). **p<0.01 vs. control. Means ± SEM...

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...

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...

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...

Various products containing rarely characterized anabolic steroids are nowadays marketed as dietary supplements. Herein, the designer steroid methyl-1-testosterone (M1T) (17β-hydroxy-17α-methyl-5α-androst-1-en-3-one) was identified, and its biological activity, potential adverse effects, and metabolism were investigated. The affinity of M1T toward...

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

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...

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 developed countries, diabetes is one of the ten most common causes of death. Post mortem diagnosis of glucose metabolism disorders can be difficult and vague because of the lack of characteristic morphological findings. Reviews of the literature are presented concerning biochemical problems in cases of unclear hyper- or hypoglycemia. After repet...