Fatal blood and tissue concentrations of more than 200 drugs.

Vitreous humor (VH) is a gelatinous substance contained in the posterior chamber of the eye, playing a mechanical role in the eyeball. It has been the subject of numerous studies in various forensic applications, primarily for the assessment of postmortem interval and for postmortem chemical analysis. Since most of the xenobiotics present in the bloodstream are detected in VH after crossing the selective blood-retinal barrier, VH is an alternative matrix useful for forensic toxicology. VH analysis offers particular advantages over other biological matrices: it is less prone to postmortem redistribution, is easy to collect, has relatively few interfering compounds for the analytical process, and shows sample stability over time after death. The present study is an overview of VH physiology, drug transport and elimination. Collection, storage, analytical techniques and interpretation of results from qualitative and quantitative points of view are dealt with. The distribution of xenobiotics in VH samples is thus discussed and illustrated by a table reporting the concentrations of 106 drugs from more than 300 case reports. For this purpose, a survey was conducted of publications found in the MEDLINE database from 1969 through April 30, 2015.

/pdf/vitreous-humor-analysis-for-the-detection-of-xenobiotics-in-3xu8hgqfjx.pdf

Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review

Purpose: To review the neuro-ophthalmological and radiological findings of acute methyl alcohol intoxication. Method: 8 acute methyl alcohol intoxication cases were evaluated. Results: All patients were male and their ages varied between 21 and 55. At the initial examination, 6 to 12 days after methanol intake, visual acuity ranged from no light perception to counting fingers at 2 meters with no color perception. Bilateral dense central scotomas were detected in patients whose vision was slightly preserved. Pupillary light reactions were either absent or sluggish. In 4 cases, edema of the optic disk and the peripapillary nerve fiber layer was observed. Three months later, optic atrophy had developed. Five patients underwent magnetic resonance imaging. Bilateral putaminal hyperintense lesions on T2 weighted images were observed in 3 cases. Two patients died and autopsy permission could not be obtained. Follow-up examination 12 months later revealed optic atrophy in the other six cases, with no improvement in vision. Conclusion: Methanol intoxication is detrimental to health, possibly resulting in blindness and occasionally death. In association with ocular signs and the other systemic and laboratory features, the ophthalmologist should be alert to the diagnosis of methanol intoxication in which visual loss may be the only symptom.

Acute blindness and putaminal necrosis in methanol intoxication

Objectives. The optimal antidote for the treatment of ethylene glycol or methanol intoxication is not known. The objective of this systematic review is to describe all available data on the use of ethanol and fomepizole for methanol and ethylene glycol intoxication. Data Source. A systematic search of MEDLINE and EMBASE was conducted. Study Selection. Published studies involving the use of ethanol or fomepizole, or both, in adults who presented within 72 hours of toxic alcohol ingestion were included. Our search yielded a total of 145 studies for our analysis. There were no randomized controlled trials, and no head-to-head trials. Data Extraction. Variables were evaluated for all publications by one independent author using a standardized data collection form. Data Synthesis. 897 patients with toxic alcohol ingestion were identified. 720 (80.3%) were treated with ethanol (505 Me, 215 EG), 146 (16.3%) with fomepizole (81 Me, 65 EG), and 33 (3.7%) with both antidotes (18 Me, 15 EG). Mortality in patients treated with ethanol was 21.8% for Me and 18.1% for EG. In those administered fomepizole, mortality was 17.1% for Me and 4.1% for EG. Adverse events were uncommon. Conclusion. The data supporting the use of one antidote is inconclusive. Further investigation is warranted.

https://downloads.hindawi.com/journals/emi/2013/638057.pdf

A Systematic Review of Ethanol and Fomepizole Use in Toxic Alcohol Ingestions

The utility of the toxicology laboratory in emergency medicine is directly related to both establishing communication between the toxicology laboratory and the clinical staff, and to providing reliable toxicology data while the diagnostic process is still in progress. When 604 patients, on whom a “complete toxicology screen” was requested, were evaluated using quantitative probes involving chemical spot tests, immunoassay, TLC and/or selected GC/HPLC methods, the resulting data were demonstrated to be of value. The ability of the clinician to accurately predict which, if any, of a large number of intoxicants were present in a given patient, was found to be minimal and as a result these combined tests were found to be essential in facilitating a proper diagnosis. Additionally, it was found that using only chemical spot tests, immunoassay and TLC in a combined qualitative approach detected 94-98% of all the substances eventually found within the population when it was further studied using more soph...

The Role of the Toxicology Laboratory in Emergency Medicine II: Study of an Integrated Approach

A 44-year-old man was found unconscious beneath an elevated rapid transit right-of-way. On admission to the emergency room, the patient was comatose in metabolic acidosis with high anion and osmolal gaps. The serum methanol was 583 mg/dL. The serum ethanol and ethylene glycol were negative. The patient was treated with ethanol, bicarbonate, and hemodialysis. He expired 40 h after admission. The postmortem methanol concentrations in body fluids were as follows: bile 175 mg/dL, vitreous humor 173 mg/dL, and blood 142 mg/dL. Urine was not available for analysis. Postmortem methanol concentrations in body tissues are given in decreasing order: brain 159 mg/100 g, kidney 130 mg/100 g, lung 127 mg/100 g, spleen 125 mg/100 g, skeletal muscle 112 mg/100 g, pancreas 109 mg/100 g, liver 107 mg/100 g, and heart 93 mg/100 g. The total amount of methanol in the gastric contents was 73 mg. Methanol determinations were performed on a Hewlett-Packard 5840A gas chromatograph with flame ionization detection using a glass column packed with 0.2% Carbowax 1500 on Carbopack C. The internal standard used was n-propyl alcohol.

Methanol intoxication: distribution in postmortem tissues and fluids including vitreous humor.

The general toxicology unknown often presents challenges and interests to toxicologists A systematic analytical approach to search for drugs or poisons is presented here The preliminary screening analyses were as follows: alcohol by gas chromatography (GC), ethchlorvynol colorimetric analysis, enzyme multiplied immunoassay technique (EMIT), basic drug screening by GC, and neutral and weakly acidic drug screening by GC Other additional analyses were performed depending on the special circumstance of each individual case and the results of these preliminary analyses Positive findings were confirmed by computerized gas chromatography/mass spectrometry when practical Quantitation was performed by GC whenever possible

The General Toxicology Unknown I. The Systematic Approach

A general toxicology unknown case is presented to demonstrate our systematic approach. A 20-year-old male was found dead with multiple suicide notes. Overdose was suspected but substances were not known. Blood alcohol was negative. Urine was analyzed by enzyme-multiplied immunoassay technique and was negative for all drugs assayed. Urine was then extracted with ethyl acetate:hexane (1:1) at pH 10 and back-extracted into 1.0N sulfuric acid. The acidic layer was adjusted to pH 10, and re-extracted with ethyl acetate:hexane (1:1). The residue was analyzed by gas chromatography (GC) on a 3% OV-101 column. It was found to be negative for all commonly screened substances. However, several unknown peaks were observed. Electron impact mass spectra of these unknown peaks were obtained and searched for in our computer library of more than 25000 mass spectra. These unknown peaks were identified as doxylamine and pyrilamine by gas chromatography/mass spectrometry. The base peak and molecular ion for pyrilamine were at m/z 121 and 285, respectively. The base peak for doxylamine was at m/z 58. No molecular ion was observed for doxylamine. Both doxylamine and pyrilamine are antihistamines, but are promoted and used in the management of insomnia. Quantitation was performed on a GC using dexbrompheniramine as an internal standard. Blood concentrations for doxylamine and pyrilamine were 0.7 and 7.0 mg/L, respectively. Concentrations in other tissues were determined. Death was caused by combined doxylamine and pyrilamine intoxication; the manner of death was suicide.

The general toxicology unknown. II. A case report: doxylamine and pyrilamine intoxication.

A method for the identification and quantitation of two tricyclic antidepressants, amoxapine (Asendin®) and trimipramine (Surmontil®) is presented here. Samples were extracted with hexane at pH 10, back-extracted with 1.0N sulfuric acid. The acidic layer was adjusted to pH 10 and re-extracted with hexane. Electron impact mass spectra were obtained. The base peak and molecular ion for amoxapine were at m/z 245 and 313, respectively. The base peak and molecular ion for trimipramine were at m/z 58 and 294, respectively. There were three forensic toxicology cases involving amoxapine in Cook County, IL, in 1980 and 1981. The concentrations of amoxapine in blood for these three cases were 1.66 mg/L, 7.16 mg/L, and 2.95 mg/L, respectively.

Analysis of blood and tissue for amoxapine and trimipramine.

A 24-year-old black female presented a live birth of six-months gestation. The 700-g neonate survived for 11 h. After toxicology revealed the presence of pentazocine and tripelennamine (T's and Blues), the mother admitted to using this combination intravenously 9 h previous to admission. Concentrations of pentazocine and tripelennamine were simultaneously determined by gas-liquid chromatography (GLC) combined with nitrogen selective detection. Analyses were performed on a 3% OV-101 column, with the added internal standard, dexbrompheniramine. Both pentazocine and tripelennamine were qualitatively confirmed by their electron impact mass spectra. Concentrations of pentazocine and tripelennamine in various fluids and tissues were determined.

M I Schaffer

Papers

Methanol intoxication: distribution in postmortem tissues and fluids including vitreous humor.

The General Toxicology Unknown I. The Systematic Approach

The general toxicology unknown. II. A case report: doxylamine and pyrilamine intoxication.

Analysis of blood and tissue for amoxapine and trimipramine.

Spontaneous live birth with a maternal history of intravenous use of pentazocine and tripelennamine (T's and blues).