A Rapid, Comprehensive Screening Procedure for Basic Drugs in Blood or Tissues by Gas Chromatography

“…All samples were extracted using a modified procedure of Foerster‐Garriott and comprehensively published . A minimum of two separate unknown sample dilutions of different volumes were used and placed in separate tubes.…”

Section: Methodsmentioning

confidence: 99%

Fatal Oral Methylphenidate Intoxication with Postmortem Concentrations

Cantrell

Ogera

Mallett

et al. 2014

Journal of Forensic Sciences

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Methylphenidate (MPD) is a widely prescribed stimulant used primarily for the treatment for attention-deficit/hyperactivity disorder (ADHD). Suicide attempts involving MPD ingestion have been well described; however, deaths attributed solely to MPD ingestion have not been reported. A 62-year-old woman was found dead on her floor. The only discrepancy in among her medication quantities was that >three hundred 10 mg MPD tablets were missing. Analysis utilizing gas chromatography-mass spectrometry revealed elevated postmortem MPD peripheral and central blood, liver and vitreous humor concentrations. Considering both the central blood to peripheral blood ratio (0.89) and the liver to peripheral blood ratio (3.3), MPD does not appear subject to significant postmortem redistribution. With no other identifiable cause of death, we report what appears to be the first isolated MPD ingestion associated with a fatality.

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“…The brains were rapidly removed and placed in ice-cold isotonic sucrose. Brains were extracted by a modification of the techniques of Osselton (9) and Foerster et al (10). Tissues were homogenized in 4 volumes (vol/wt) of 1 M Tris base (pH 10.9) with alkaline protease (1 mg/g of tissue) by using a Brinkmann Polytron (setting 6.5, 30 sec).…”

Section: Methodsmentioning

confidence: 99%

Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy.

Basile

Pannell

Jaouni

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Brain extracts from rats with hepatic encephalopathy due to thioacetamide-induced fulminant hepatic failure contained 4-to 6-fold higher concentrations of substances that inhibit radioligand binding to benzodiazepine receptors than corresponding control rat extracts. Both isocratic and gradient-elution HPLC indicated that this inhibitory activity was localized in 3-8 peaks with retention times corresponding to deschlorodiazepam, deschlorolorazepam, lorazepam, oxazepam, diazepam, and N-desmethyldiazepam. The presence of diazepam and N-desmethyldiazepam was confirmed by mass spectroscopy. Both mass spectroscopic and radiometric techniques indicated that the concentrations of N-desmethyldiazepam and diazepam in brain extracts from encephalopathic rats were 2-9 and 5-7 times higher, respectively, than in control brain extracts. While benzodiazepines have been identified previously in mammalian and plant tissues, this report demonstrates that concentrations of these substances are increased in a pathophysiological condition. These findings provide a rational basis for the use of benzodiazepine receptor antagonists in the management of hepatic encephalopathy in humans.Hepatic encephalopathy (HE) is a complex neuropsychiatric disorder arising from the metabolic abnormalities associated with acute or chronic liver failure (1). It has been proposed that an increase in the activity of y-aminobutyric acid (GABA)-containing pathways contributes to the manifestations of this disorder (2). Studies of visual evoked responses in the galactosamine-treated rabbit model of HE due to fulminant hepatic failure (FHF) (3) and in rats with HE due to thioacetamide (TAA)-induced FHF (4) indicate that central nervous system (CNS) GABAergic tone is increased in these models of HE. Electrophysiologic studies of single cerebellar Purkinje neurons in the rabbit model of HE further support this hypothesis. These neurons are hypersensitive to depression by the GABA receptor agonist muscimol and the benzodiazepine (BZ) receptor agonist flunitrazepam, but not to the a-adrenergic receptor agonist phenylephrine (5). In contrast, BZ receptor antagonists increase the spontaneous firing rate of these neurons and reverse their hypersensitivity to muscimol at concentrations that do not affect the firing rates of control neurons (5). Furthermore, BZ receptor antagonists correct the abnormalities in visual evoked responses associated with HE while transiently reversing the behavioral manifestations of this syndrome in both the rabbit and rat models of this disorder (3, 4).These observations indicate that the increase in "GABAergic tone" found in HE may be mediated by the BZ receptor, possibly as a consequence of an increase in the concentration or availability of a BZ receptor ligand with agonist (BZ-like) properties (6, 7). Elevated concentrations of substances that competitively and reversibly inhibit radioligand binding to BZ receptors have recently been found in extracts of brain and peripheral tissues from the TAA-treated rat model of HE (8)....

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A Rapid, Comprehensive Screening Procedure for Basic Drugs in Blood or Tissues by Gas Chromatography

Cited by 144 publications

References 4 publications

Detection of synthetic cathinones in victims of sexual assault

Detection of synthetic cathinones in victims of sexual assault

Fatal Oral Methylphenidate Intoxication with Postmortem Concentrations

Brain concentrations of benzodiazepines are elevated in an animal model of hepatic encephalopathy.

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