Ronald C. Backer

FATAL FENTANYL INTOXICATION FOLLOWING EXCESSIVE TRANSDERMAL APPLICATION

The case history and toxicological findings of a fatal fentanyl intoxication due to the application of multiple transdermal patches are presented. An 83 year-old white female with terminal cancer was found dead with three 100 mg/h fentanyl patches on her chest. The autopsy and subsequent histological studies revealed extensive areas of gastric carcinoma, a large atrial tumor, ulceration of esophagus, metastasis of peripancreatic lymph nodes and a recent surgical removal of part of the lower lobe of the left lung. Toxicological analysis by GC/MS yielded fentanyl concentrations of blood, 25 ng/mL; brain, 54 ng/g; heart 94 ng/g; kidney 69 ng/g; and liver 104 ng/g. The cause of death was determined to be fentanyl overdose and the manner of death was ruled undetermined as the investigation was unable to conclusively establish whether this was an accidental overdose, a suicide, an assisted suicide, or possible a homicide. This case demonstrates the need for caution in self-administration of transdermal fentanyl patches, in particular, the dangers inherent in the application of multiple patches which can result in the release of potentially toxic or lethal doses.

The comparison of alcohol concentrations in postmortem fluids and tissues

Fluid-tissue/blood alcohol ratios were calculated for a number of cases. The use of such factors to determine the blood alcohol concentration (BAC) becomes important when a blood specimen is not available or is contaminated. It was shown that estimates of blood alcohol concentrations derived from other physiological fluids or tissues can only be expressed as lying within a wide concentration range. Estimations of the BAC can be improved by using the stomach alcohol concentrations to determine if the decreased was in an absorption or postabsorption phase at the time of death.

1,1,1-Trichloroethane: Report of a Fatal Intoxication

TCE was indicated in the accidental death of a woman cleaning up a paint spill in an enclosed, poorly ventilated room. Blood and tissue concentrations of TCE were measured by head-space gas chromatography. The concentrations found were compared with previously reported concentrations concluding that the demonstrable presence of TCE in blood at a concentration above 1.0 to 1.5 mg/100 ml would be consistent with death. However, the rapid dissipation of TCE from blood dictates that its presence in post mortem samples at any concentration must be considered as a factor in determining the cause of death.

Detection of Drugs Using XAD-2 Resin. I: Choice of Resin, Chromatographic Conditions, and Recovery Studies

Amberlite XAD-2, a nonionic polystyrene divinylbenzene resin, was first used for the analysis of drugs in urine and a number of reports have described the development at optimal conditions for extraction, including type of resin columns, pH conditions, and eluting solvents. XAD-4 and XAD-7 resins were compared to the similarly structured XAD-2 resin and no significant advantage over the XAD-2 resin for drug screening was observed. A quantity of 5 to 6 g of resin was found to have sufficient capacity for the extraction of 200 ml of pentobarbital solution (1 mg/100ml). A column flow rate of approximately 15 ml/min (gravitational flow) was sufficient for analysis and slower rates were not more efficient. A mixture of ethyl acetate and 1,2-dichloroethane (3:2) was found to give best overall recovery (66 to 94%) of drugs, the resulting extracts being reasonably free of interfering substances. A pH value of 8.5 is recommended as optimum for comprehensive analysis of acidic and basic drugs. Recovery studies were conducted on spiked samples to determine drug losses occuring during various steps in the XAD-2 extraction procedure for four acidic (amobarbital, secobarbital, pentobarbital, and phenobarbital) and four basic (morphine, codeine, meperidine, and methadone) drugs. A relatively small amount (0 to 5%) of the drugs was not adsorbed by the resin and amounts varying from 6 to 40% failed to be desorbed by the eluting solvent. Additional losses occurred during the removal and analysis of TLC spots. Recovery of drugs from aqueous solutions analyzed with the XAD-2 resin were compared to recoveries reported in the literature with other XAD-2 resin methods for the extraction of drugs from urine. Recovery of phenobarbital, morphine, and codeine improved by 4 to 23% while recoveries of amobarbital, pentobarbital, secobarbital, methadone, and meperidine were 4 to 28% less efficient when compared to literature data.

Gas chromatography-mass spectrometry of fluorocarbons 11 and 12 in biologic specimens.

Fluorocarbons 11 and 12 were detected and identified in tracheal air, blood, liver, lung, and brain specimens by head-space analysis utilizing a GC-MS. The individual spectrum for each of the fluorocarbons was obtained. The method is easily adaptable to other volatiles.

Detection of drugs using XAD-2 resin. II:Analysis of liver in medical examiner's cases.

Liver tends to concentrate drugs in quantities generally higher than those found in blood or other body compartments. This fact as well as the general availability of liver in postmortem cases makes it an important specimen for comprehensive toxicologic investigation. A scheme for the analysis of liver for drugs with tissue hydrolysis, XAD-2 resin extraction, and TLC has been developed and the parameters affecting recovery have been studied. The hydrolysis of liver specimens at various pH conditions resulted in an improved recovery for morphine by using pH 2 (2N hydrochloric acid). Recoveries of barbiturates, codeine, and meperidine were essentially the same at pH 2 and pH 3. A considerable loss (22 to 55%) was observed for four drugs (pentobarbital, morphine, codeine, and meperidine) as a result of drug binding to the tissue pellets during the process of centrifuging the liver homogenates. This method is recommended as a comprehensive screening procedure for drugs in liver tissue. For quantitative purposes, however, it is necessary to determine a correction factor for all the losses occurring at the various steps of the procedure. This procedure compared favorably with other procedures for liver analysis reported in literature.

Thiopental Suicide-Case Report

Thiopental was indicated in the suicide death of a hospital employee. The blood thiopental level was determined to be 27.9 mg% by ultraviolet spectrophotometry, and positive identification was accomplished using gas chromatography, thin-layer chromatography, and infrared spectrophotometry.

Detection of Drugs Using XAD-2 Resin. III: A Routine Screening Procedure for Bile

The ability of bile to concentrate drugs and metabolites coupled with its general availability make it suitable for analysis and often the fluid of choice in postmorten cases requiring drug screening. Bile (5 to 10 ml) was diluted with water, sulfuric acid was added, and the mixture was autoclaved. The precipitated bile salts were easily removed by filtration and the filtrate (pH adjusted to 8.0 to 8.5) extracted with XAD-2 resin. Drugs were eluted with a mixture of ethyl acetate/1,2-dichloroethane and analyzed with thin-layer chromatography. Varying the dilution of bile improved the recovery of morphine, codeine, methadone, amobarbital, and phenobarbital. Excessive dilution, however, caused a washing phenomenon and reduced recovery of some drugs, as shown with morphine and codeine. The procedure described is useful for the rapid screening of bile specimens for drugs.