Biomedical subjects
Publications and source records attributed to Y H Caplan.
A case is reported where the death of an individual resulted from the ingestion of diflunisal. Diflunisal was identified by a combination of liquid chromatography, UV spectrophotometry and colorimetry. Diflunisal was quantified in blood (260 mg/l), bile (71 mg/l), kidney (350 mg/kg), liver (400 mg/kg), stomach contents (34 mg) and urine (78 mg/l). No previous literature references discussing diflunisal related fatalities were available.
We studied the recently developed Abbott fluorescence polarization immunoassay (FPIA) for amphetamine and methamphetamine in urine and compared the results with those of the Syva enzyme-multiplied immunoassay technique (EMIT) and a gas-chromatographic assay. The FPIA method showed a limit of quantification of 0.3 mg/L, comparable with the lower cutoff of the EMIT assay. FPIA demonstrated greater specificity than the EMIT assay: phenylpropanolamine and ephedrine showed extremely limited cross reactivity with the FPIA antibody. Analysis of 249 urine specimens by all three methods clearly demonstrated the FPIA method to be acceptable for screening for amphetamine and methamphetamine in urine.
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We adapted the reagents from 11 different enzyme-multiplied immunoassay technique (EMIT; Syva Co., Palo Alto, CA 94304) drug-detection kits for use in a centrifugal analyzer. The antibody reagents were mixed into a single dilute solution, and the enzyme-labeled drug derivatives were combined similarly (Mixed EMIT reagents), for use in testing urine samples for the presence of multiple drugs. The assay, a rapid comprehensive drug-screening technique, requires 100 microL of sample and is capable of testing seven samples, in duplicate, simultaneously, in less than 10 min. Clinical evaluation (n = 325) by comparison with thin-layer chromatography (TLC) had the following results: 230 samples were negative by TLC and Mixed EMIT, 77 samples were positive by TLC and Mixed EMIT, 16 samples were negative by TLC and positive by Mixed EMIT, and two samples were positive by TLC and negative by Mixed EMIT.
In vitro accuracy and precision studies were conducted using silica gel, magnesium perchlorate, and indium encapsulation breath collection tubes in conjunction with three infrared breath ethanol analyzers (BAC Verifier, Intoxilyzer 5000, and Intoximeter 3000), the Breathalyzer 900A, and the GC Mark IV. Statistical analyses revealed good accuracy and precision and correlation between direct and delayed vapor ethanol analyses for each combination of instruments and collection devices (range = 0.000 to 0.250 g/210 L, N = 42/instrument, r greater than 0.99). Delayed vapor ethanol analysis utilizing each instrument and collection device combination appears to predict satisfactorily original vapor ethanol concentrations.
In a preliminary study to determine the applicability of the Abbott radiative energy attenuation (REA) method for the quantification of ethanol in whole blood specimens it was concluded that a larger number of samples was required to evaluate the method, particularly for use in forensic toxicology applications. In this study, 573 blood specimens from suspected driving while intoxicated individuals (DWI blood) and 532 postmortem blood specimens (PM blood) were analyzed by the REA method and a headspace gas chromatographic method (GC) currently used in this laboratory. "Negative" specimens (less than 10 mg/dL by GC) and "positive" specimens (greater than or equal to 10 mg/dL by GC) in each category were analyzed. Linear regression analysis comparing the REA values with the GC values was performed for each type of blood specimen. The equation obtained for DWI blood specimens was REA = 0.943 GC + 1.54; the equation for PM blood specimens was REA = 0.980 GC + 2.76. The correlation coefficient for each group was greater than 0.99. The data suggested that a limit of detection of 10 mg/dL could be applied for DWI blood specimens, while 20 mg/dL would be recommended as the limit of detection for PM blood specimens.
Eleven incidents of carbon monoxide (CO) intoxication resulting in sixteen fatalities are reported. All of the cases involved heating systems as either the source or the means of distributing the CO. Blood samples were analyzed for ethanol and CO. Elevated blood CO saturations were found in 14 of the 16 victims while none of the victims had a blood ethanol concentration greater than 0.10% (w/v).
The in vitro accuracy and precision of four infrared breath-alcohol analyzers, the Alcotest 7010, BAC Verifier, Intoxilyzer 5000, and Intoximeter 3000, were studied with a protocol adapted from portions of the U.S. Department of Transportation's (DOT) "Standard for Devices to Measure Breath Alcohol." Statistical evaluation of these studies indicated that all instruments met or exceeded the performance requirements modified from the U.S. DOT Standard for quantitative evidential breath-alcohol analyzers.
The incidence of drug and chemical related deaths was studied over a six-year period in the State of Maryland. Deaths were classified into the following categories: alcohol, carbon monoxide (CO), single drugs, multiple drugs, and narcotism. The last three categories were further subdivided as to the specific drugs or chemicals involved. Over the six-year period the number of alcohol and CO deaths remained steady, the number of barbiturate and propoxyphene deaths declined, while the number of tricyclic antidepressant drug deaths increased.
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Ninety Breathalyzer instruments (Model 1000) and twenty instruments (Models 900, 900A) were studied using a protocol described by the Department of Transportation's "Standard for Devices to Measure Breath Alcohol." Although the mean of each of three concentrations tested (0.05, 0.10, and 0.15 g/210 L) compared favorably in both series, the standard deviation was consistently higher for the Model 1000 instruments. The Model 1000 instruments also produced a significant number of test results which exceeded the normally expected scientific deviation.
A case is presented where phentermine, a sympathomimetic amine used as an anorectic drug, is believed to have significantly contributed to the death of an individual in whom other drugs were also found. Blood, urine, and tissue concentrations of phentermine are reported and compared to other cases in the literature.
A total of 1859 cases provides the basis for this study in which propoxyphene, and often its major metabolite, was demonstrated by toxicological analysis in the blood or tissues of the deceased at 27 medical examiner or coroner's offices across the United States and Canada. The study period includes the last five months of 1975 through December 1978. The cases describe a clearly defined adult population with a marked tendency toward hypochondria, chronic minor illness, and severe psychiatric problems. The high proportion of suicides (44.1% of the total cases and 54.0% of the drug-caused deaths) and multiple-drug toxicities (88.6%) suggests that the involvement of propoxyphene in many of these fatalities may be of less significance than the phenomenon of "polypharmacy" and self-medication without appropriate medical supervision. This evaluation of propoxyphene provides no evidence that propoxyphene is responsible for "street-drug" fatalities. Its appearance in postmortem toxicological examinations has been declining sharply since 1977, but it continues to be dangerous when used excessively, particularly in combination with alcohol and other central nervous system depressant drugs.
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.
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.
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.
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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.