Several families of higher fungi contain mycotoxins that cause serious or even fatal poisoning when consumed by humans. The aim of this review is to inventory, from an analytical point of view, ...poisoning cases linked with certain significantly toxic mycotoxins: orellanine, α- and β-amanitin, muscarine, ibotenic acid and muscimol, and gyromitrin. Clinicians are calling for the cases to be documented by toxicological analysis. This document is therefore a review of poisoning cases involving these mycotoxins reported in the literature and carries out an inventory of the analytical techniques available for their identification and quantification. It seems indeed that these poisonings are only rarely documented by toxicological analysis, due mainly to a lack of analytical methods in biological matrices. There are many reasons for this issue: the numerous varieties of mushroom involved, mycotoxins with different chemical structures, a lack of knowledge about distribution and metabolism. To sum up, we are faced with (i) obstacles to the documentation and interpretation of fatal (or non-fatal) poisoning cases and (ii) a real need for analytical methods of identifying and quantifying these mycotoxins (and their metabolites) in biological matrices.
Although blood is the reference medium in the field of forensic toxicology, alternative matrices are required in case of limited, unavailable or unusable blood samples. The present review ...investigated the suitability of bone marrow (BM) as an alternative matrix to characterize xenobiotic consumption and its influence on the occurrence of death. Basic data on BM physiology are reported in order to highlight the specificities of this matrix and their analytical and toxicokinetic consequences. A review of case reports, animal and human studies involving BM sample analysis focuses on the various parameters of interpretation of toxicological results: analytic limits, sampling location, pharmacokinetics, blood/BM concentration correlation, stability and postmortem redistribution. Tables summarizing the analytical conditions and quantification of 45 compounds from BM samples provide a useful tool for toxicologists. A specific section devoted to ethanol shows that, despite successful quantification, interpretation is highly dependent on postmortem interval. In conclusion, BM is an interesting alternative matrix, and further experimental data and validated assays are required to confirm its great potential relevance in forensic toxicology.
A 20‐year‐old man, a cocaine addict and regular ecstasy user, with a medical history of allergic asthma died after ingesting half a tablet earlier the same day. The white tablet, stamped with a ...“smiling sun” logo looked very much like an ecstasy tablet and was sold as such. He experienced a severe asthma attack just after ingesting the half tablet and it evolved over the next few hours into fatal cardiorespiratory arrest. Biological samples, taken after embalming, were analyzed by high‐performance liquid chromatography tandem mass spectrometry (HPLC‐MS/MS). Analysis revealed meta‐chlorophenylpiperazine (mCPP) in concentrations of 45.8 mg in a similar tablet obtained later from the drug dealer, 5.1 ng/mL in the bile, 0.3 ng/g in the liver, 15.0 ng/mL in the urine, and its absence in a hair sample (<0.02 ng/mg), which indicated he was not a regular user (whereas strong concentrations of MDMA and cocaine were found in the hair). Interrogated by the police after his arrest, the dealer said that he had sold the victim and for the very first time two tablets with the same “smiling sun” logo. The tablet used for analysis was from the same brand as the one ingested by the victim. The autopsy excluded other causes of death, while the histological analyses showed a large number of polynuclear eosinophils in the bronchial walls, confirming the asthmatic pathology. None of the other organs examined (larynx, liver, heart, adrenal glands, and kidneys) showed any distinctive signs, and in particular no inflammatory infiltrate. The death was the result of an asthma attack in an asthmatic person, violently decompensated following ingestion of approximately 20 mg of mCPP.
•A case of suicide with a “non-lethal” self-defense firearm is described.•The hemorrhage trauma of the aero digestive crossroad leaded to death.•Awareness about the morbid and lethal potential of ...these weapons is needed.
Rubber bullets weapons can have tragic consequences when used at short range and on vulnerable body areas. A man in his forties was found deceased at his house, covered in blood. A “non-lethal” firearm was found near the bed: the «SAPL GC27». This is a single shot handgun with mini Gomm Cogne ammunition: 12 rubber spherical pellets, 7.4 mm in diameter. The findings were consistent with an intra buccal shot, and an ingestion-inhalation of blood and projectiles. Cause of the death was linked to both the hemorrhage due to mouth and aero digestive crossroad trauma, responsible of a mechanical asphyxia, and blood absorption in lungs. This case insists on the deadly potential of this weapon if misused. Fortunately, the term “non-lethal” has been progressively replaced, but sometimes still can be seen, especially in gunsmith and webstores. It should be deleted to avoid confusion among inexperienced people, and at best, this weapon should be restricted to certain professions.
Abstract We reported on the death by poisoning of a one-month-old baby that had followed the death of one of her sister (due to cyamemazine overdose). Exhumation of the corpse was done 8 months after ...burial and revealed the presence of amitriptyline. Parent drug and its metabolite were analysed by HPLC–MS/MS in positive ionisation mode on a C18 analytical column using a gradient of acetonitrile and 2 mM formate buffer at pH = 3. Quantification is based on the main ion m / z = 233, the common product ion of nortriptyline (MH+ , m / z 264), amitriptyline (MH+ , m / z 278) and nortriptyline D3 used as internal standard (MH+ , m / z 267). Amitriptyline and nortriptyline in the liver were measured at a concentration of 29.8 and 3.6 μg/g, respectively. Hair analyses revealed the presence of amitriptyline and nortriptyline at concentrations of 1811 and 43 pg/mg, respectively, while complementary analyses showed the presence of bromazepam in the hair at a concentration of 740 pg/mg, thus documenting previous administrations. The mother confessed later having used the drinkable form of the pharmaceutical LAROXYL® by pouring the content of a 20 ml bottle (at 40 mg/ml) into the feeding-bottle of her child. The milk was sweet but still bitter and following the testimony of a close relative, the whole family helped to feed the crying baby.
The authors have reviewed the main toxic plants responsible for human deaths throughout the world. Forty plants (genera or species) were listed in order to establish an inventory of the active ...molecules that could be identified, the already published analytical methods and the reported human fatal cases. In a second step, the authors have developed a general method for the detection of various toxins in whole blood by high-performance liquid chromatography coupled to mass spectrometry or tandem mass spectrometry. Sample preparation was realized by liquid–liquid extraction at pH 9.5 for oleandrine, taxol and the alkaloids. These latter compounds were divided into two groups following their chemical properties and could be subsequently purified by acid/base clean up. Cyanogenic compounds and atractyloside were isolated by precipitation of the protein content with acetone and purified for atractyloside by washing with chloroform. Separation of the drugs occurred under reversed-phase conditions on a C
18 analytical column 150×2 mm I.D. (5 μm particle size) using two different mobile phases. The first one, formiate buffer 2 m
M acidified at pH 3.0, was used for the separation of atractyloside, oleandrine, taxol, the cyanogenic molecules and some alkaloids. The second mobile phase, formiate buffer 10 m
M made basic at pH 8.2 was used for the majority of other alkaloids. A gradient elution mode was chosen using acetonitrile or acetonitrile–methanol (50:50, v/v) as the eluting solvent. Detection under positive ionization mode was the mode of choice for all compounds except for atractyloside (negative ions) and for taxol (mixed mode available). Application to real forensic cases has been demonstrated.
A fatal intoxication case involving ropinirole Duband, Sébastien, MD; Bidat, Carolyne, MD; Gaillard, Yvan, PharmD ...
Journal of forensic and legal medicine,
10/2012, Volume:
19, Issue:
7
Journal Article
Peer reviewed
Abstract Ropinirole, a specific non-ergoline dopamine D2-receptor agonist, belongs to the drugs applied in treatment of Parkinson's disease (PD) and restless legs syndrome (RLS) and acts as a D2, D3, ...and D4 dopamine receptor agonist with highest affinity for D3. Therapeutic ropinirole plasma levels in adults are defined between 0.4 and 6 ng/mL. This case report documents a fatal intoxication involving ropinirole. Information about lethal ropinirole concentrations is hitherto lacking in the literature and the assessed ropinirole levels of this case may present a step towards defining potentially lethal concentrations. A 37-year-old man without medical history was found dead in a converted van used as place of residence and an autopsy was performed. The pathological findings did not reveal an apparent cause of death but the toxicological analysis revealed the presence of ropinirole, paracetamol, and alcohol in the peripheral blood sample. Quantitative analysis revealed that ropinirole was present at a peripheral blood concentration of 64 ng/mL. The ropinirole concentrations determined in vitreous humor, urine and bile were respectively, 11 ng/mL, 2670 ng/mL and 826 ng/mL. Paracetamol was detected at a blood level of <2 μg/mL. Based on the autopsy findings and toxicological results, the cause of death was primarily attributed to intoxication with ropinirole in combination with alcohol.
Testing hair for pharmaceuticals Gaillard, Yvan; Pépin, Gilbert
Journal of Chromatography B: Biomedical Sciences and Applications,
10/1999, Volume:
733, Issue:
1
Book Review, Journal Article
Peer reviewed
More than hundred pharmaceuticals, drugs of abuse or doping agents have been reported to be detectable in human hair. This article reviews the analysis of 90 drugs and drug metabolites by ...chromatographic procedures, including the pretreatment steps, the extraction methods, the reported limits of detection and the measured concentrations in real human hair samples. Some progress is observed in the detection of low dose drugs, like fentanyl or flunitrazepam. The general tendency in the last years, to highly sophisticated techniques (GC–MS–NCI, HPLC–MS, GC–MS–MS) illustrates well this constant fight for sensitivity. Some new findings, based on the recent experience of the authors, are also added.
Today, new psychoactive substances (NPS) producers increasingly appear to be targeting new synthetic opioids (NSOs), and the recent emergence of NSOs is causing considerable concern in North America ...and in Europe. For toxicologists, NSO detection in a forensic context presents three additional difficulties to the general NPS analytical detection challenge: (i) high frequency of new products, (ii) low concentrations (in μg/L range and under) in biological samples related to their high opioid potency, and (iii) extensive metabolism. In this context, the present work aims to highlight the relevance of NSO metabolite detection in potential intoxication cases. Illustration is given with U-47700, an emerging NSO, (i) that was identified in a powder recently collected in France and in a fatality case, (ii) whose metabolites were in vitro produced using human liver microsomes and their mass spectra (MS) added in our MS/MS and HRMS libraries, and (iii) for which metabolism data were compared to those of the literature: U-47700 was identified in the powder and at 3040 μg/L in peripheral blood in the fatality case. In addition, high amounts of several U-47700 metabolites, especially
N
-desmethyl-U-47700, were observed in urine. Even if metabolite formation may largely depend on the enzymatic activity as well as on the length of the survival time, confrontation of these results to data found in the literature strongly suggests that this metabolite is regularly a better blood and (mainly) urine biomarker of U-47700 intake than U-47700 itself. Indeed, in this fatality and in other previous reports,
N
-desmethyl-U-47700 produced the main observed chromatographic signal (i) systematically in vitro and (ii) commonly in vivo, especially in urines.
N
,
N
-Didesmethyl-U-47700 is also sometimes a better biomarker of U-47700 intake than U-47700 itself. Accordingly, we suggest adding
N
-desmethyl-U-47700 (and
N
,
N
-didesmethyl-U-47700) in mass spectrum databases used for toxicological screening in order to reduce the risk of false-negative results in intoxication cases involving U-47700.
PDF
