Fatal blood and tissue concentrations of more than 200 drugs.

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

During the investigation of aviation accidents, postmortem specimens from accident victims including blood, urine, and tissue are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. The first, and perhaps most important, step in the analysis process is the initial screening of biological specimens for illicit, medically prescribed, and over-the-counter compounds that may be present and potentially be a cause and/or factor in the accident. Currently, our general unknown screening (GUS) procedure involves, in part, both gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) with both diode-array detection (DAD) and fluorescence detection. Both GC and LC techniques have inherent limitations that prevent the detection of certain types of compounds. The decreased specificity and sensitivity of LC-DAD has been an impediment to the existing GUS procedure. Therefore, our laboratory set out to develop and validate an LC-MS-MS procedure that is superior to LC-DAD. The limits of detection of 359 forensically important xenobiotics have been established following solid-phase extraction from whole blood and analysis by LC-MS-MS. Although whole blood was used as the matrix during instrument validation, the method has been successfully applied to both forensic urine and tissue specimens as well.

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The screening of forensic blood, urine, and tissue specimens for xenobiotics using ion-trap liquid chromatography-tandem mass spectrometry.

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.

A 27-year-old male died as the result of swallowing a bag of cocaine. Using gas chromatography and ultraviolet spectrophotometry, the concentration of cocaine was determined on all specimens submitted for analysis. These analyses revealed what may possibly be the highest concentrations of cocaine ever reported In the toxicology literature. These values were confirmed by another medical examiner toxicology laboratory.

Sudden death due to ingestion of cocaine.

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.

M. L. Kurland

Papers

The General Toxicology Unknown I. The Systematic Approach

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