Biomedical subjects
Publications and source records attributed to Y H Caplan.
A case is presented where an individual ingested a fatal dose of chloral hydrate. Trichloroethanol (TCE), the metabolite of chloral hydrate, was initially identified by the Fujiwara reaction and quantified by gas chromatography/mass spectrometry in blood )127 mg/l), urine (128 mg/l) and stomach contents (25 mg total).
A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l.
A case is presented of a 26-year-old female who died as a result of cocaine intoxication. A blood cocaine concentration of 330 mg/l, about 1.5 times greater than the highest concentration previously reported, was found. Blood benzoylecgonine and ecgonine methyl ester concentrations were 50 and 18 mg/l, respectively. The unusually high blood concentrations of cocaine and the metabolites are suggestive of a massive administration, however, the history suggests a series of recreational uses. The manner of death was undetermined.
A case is presented of a 35-year-old black African male anesthesiology resident, found dead in his apartment. At the scene a syringe, butterfly intravenous line and a bottle of Versed (Midazolam) were recovered. A comprehensive screen for common drugs of abuse and therapeutic agents failed to detect any drugs in blood and urine. The blood ethanol concentration was 0.06 g/dl. A GC/MS SIM assay for midazolam was developed. A sub-therapeutic midazolam blood concentration of 7.5 ng/ml was detected and concentrations (ng/ml or ng/g) in bile, urine, and liver were 3.3, 7.5, and 96, respectively. The syringe fluid was then analyzed and found to contain only fentanyl, midazolam was absent. The blood fentanyl concentration was 4.9 ng/ml which is consistent with those reported in fentanyl fatalities. Fentanyl concentrations (ng/ml or ng/g) in bile, urine, and liver were 8.8, 5.0, and 5.9, respectively. The cause of death was ruled to be fentanyl intoxication and the manner of death undetermined.
Specimens of liver were collected from 40 cases in which the cause of death had been determined to be opiate intoxication. Rearings of Calliphora vicina larvae were then promoted on the decomposing liver. A control group of 10 decomposed liver specimens from non-opiate deaths was treated similarly. Analysis of larvae and liver for opiates (morphine) was conducted by radioimmunoassay. Good qualitative and quantitative correlation was observed in both the positive and negative groups. Regression analysis comparing the concentrations of opiates found in the larvae with those found in the liver in the positive group resulted in a correlation of r = 0.790.
A 28-year-old white male medical student was found hanging by the neck from the bathroom closet of a hotel room. An intravenous infusion line leading from a bottle of thiamylal sodium (an ultrashort-acting barbiturate) was inserted into the antecubital vein of the left arm. Blood was analyzed for alcohol and other volatiles and for acidic, basic, and neutral drugs. Only thiamylal was detected. Thiamylal was quantified by high-performance liquid chromatography with ultraviolet detection, and its presence was confirmed by gas chromatography/mass spectrometry. The tissue distribution of thiamylal was 29 mg/L in blood, 1.4 mg/L in urine, 16 mg/L in bile, 135 mg/kg in liver, 25 mg/kg in kidney, and 0.4 mg in the stomach contents. The uptake and distribution of thiamylal is similar to thiopental. The distribution of the drug in this case was compared to that of other fatalities involving ultrashort-acting barbiturates.
Explore the source record for details and available documents.
A case is reported where phenol, a disinfectant, was ingested and resulted in the death of a 40-year-old white female. Concentrations of phenol were determined in blood (130 mg/L), urine (47 mg/L), bile (187 mg/L), brain (486 mg/kg), kidney (331 mg/kg), muscle (204 mg/kg), liver (228 mg/kg), and stomach content (668 mg) and compared to other cases reported in the literature.
Explore the source record for details and available documents.
Cannabinoid use was studied in a nonspecific population of postmortem urine specimens in the State of Maryland. Of 500 sequential specimens screened for cannabinoids by enzyme multiplied immunoassay EMIT, 63 (13%) were initially positive and 58 (12%) were confirmed positive (92%). It was observed that geographic location and race did not correlate with cannabinoid prevalence. Cannabinoid use was observed to be strongly age related, with peak use by the 21- to 25-year-old age group where 22% of the cases were positive. Use of cannabinoids was also closely linked to homicides, which represented nearly half of the positive cases but only 13% of the total cases. When comparing manner of death, the greatest percent of confirmed positives was seen in homicide (26%) and drug-related (17%) deaths. The incidence of cannabinoid use was found to be more than 3 times as great in drug-related (17%) as compared to natural deaths (5%). The percent of cannabinoid-positive cases from vehicle-related accidents was low (6%) and that from nonvehicle-related accidents somewhat higher (10%). Other drugs appeared in cannabinoid-positive cases. Most prevalent was ethanol N = 18, followed by morphine (from heroin, N = 11), quinine N = 11, and cocaine N = 11. Phencyclidine (PCP) occurred twice and several other drugs were reported only once. Of the 25 homicide cases screened for drugs, 64% were positive for some drug including ethyl alcohol. Thus it appears that a high percentage of homicide cases are drug related. Males greatly outnumbered females (56:2) in positive cases, but the number of female specimens received was small.
Explore the source record for details and available documents.
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.
Explore the source record for details and available documents.
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.
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.