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Biomedical subjects

Y H Caplan

Publications and source records attributed to Y H Caplan.

At least 19 recordsLinked to original sources
PubMed2000

The characterization of human urine for specimen validity determination in workplace drug testing: a review.

One challenge facing the laboratory forensic toxicologist today is verifying the validity of the random urine specimen submitted for workplace drugs of abuse analysis. Determining whether urine substitution has occurred is best accomplished through the inspection of the specimen's appearance and the performance of specific laboratory tests, such as determining the concentration of biochemical metabolic waste products and measuring indices of urine concentration. Criteria for classifying submitted urine as substituted are postulated after an extensive review of the published scientific literature. Relevant studies that were evaluated include normal random urine reference interval studies, clinical studies involving the analysis of random urine specimens, theoretical dilutional limits, medical conditions resulting in overhydration, and water-loading studies. After compilation of the study data, derived substituted criteria of urinary creatinine < or = 5.0 mg/dL and urinary specific gravity < or = 1.001 are suggested. A urine specimen meeting these criteria may be considered substituted because it is not consistent with the clinical characteristics associated with normal human urine.

Humans↗
PubMed1998

Detection of methadone, methadone metabolites, and other illicit drugs of abuse in hair of methadone-treatment subjects.

The disposition of methadone, its metabolites, and other illicit drugs of abuse was investigated in head hair samples collected from heroin users (N = 20) enrolled in an outpatient detoxification study. Hair samples were assayed for methadone, methadone primary metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, EDDP), methadone secondary metabolite (2-ethyl-5-methyl-3,3-diphenylpyrroline, EMDP), cocaine, phencyclidine, heroin, and 6-acetylmorphine. Hair samples were cut, washed, and incubated in methanol. The methanolic hair wash and incubation fractions were purified with solid-phase extraction and assayed by gas chromatography-mass spectrometry. Methadone, methadone metabolites, cocaine, and phencyclidine were assayed quantitatively, and other drugs were measured qualitatively. The number of positive results and the corresponding concentration ranges were as follows: methadone, 0-15.0 ng/mg (N = 18); EDDP, trace (N = 13); EMDP, trace (N = 1); cocaine, 0->40 ng/mg (N = 14); phencyclidine, 0-1.5 ng/mg (N = 2); heroin, positive (N = 3); and 6-acetylmorphine, positive (N = 4). These data suggest that testing hair for methadone, methadone metabolites, and other illicit drugs of abuse may be useful to drug-treatment specialists as a means of verifying drug-use history, monitoring compliance, and providing a broad measure of drug exposure.

Gas Chromatography-Mass Spectrometry↗
PubMed1996

The storage of forensic urine drug specimens as dry stains: recovery and stability.

The feasibility of storing forensic urine drug specimens as dry stains on Whatman #3 paper was studied by evaluating the stability of the drugs and recovery from the stains. Drug stains prepared from urine (3 mL) were stores at -20 degrees C, 4 degrees C, and at room temperature for a period of 12 weeks. The study included: amphetamine, benzoylecgonine, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), morphine, and phencyclidine (PCP) as examples of the HHS regulated drug classes. Drugs were eluted from the stains as follows: methanol:saline (1:1) for PCP and THC-COOH, saline for benzoylecgonine and carbonate/bicarbonate buffer pH 9.2 for amphetamine and morphine. Stains were eluted from the support matrix (Whatman #3 filter paper), extracted and analyzed by gas chromatography/mass spectrometry. All drugs were stable under all of the storage conditions except the THC-COOH urine stain stored at room temperature that degraded to zero after 12 weeks. Therefore, drug stains when kept frozen or refrigerated appear to provide a viable means for storing positive urine specimens.

Drug Stability↗
PubMed1994

Fluoxetine and violent death in Maryland.

A retrospective Medical Examiner case review of all deaths in Maryland where either fluoxetine or tricyclic antidepressant (TCA) use was forensically detected was conducted for the time period January 1987-July 1991. Case records and toxicology reports from the Office of the Chief Medical Examiner were reviewed to determine cause and manner of death, circumstances of death, demographic information on the decedent, prior medical history of the decedent, and presence and level of either fluoxetine or TCA in various body fluids/tissues. Suicide was the manner of death most frequently associated with TCA and fluoxetine detection. Violent methods were more often associated with fluoxetine suicides than with TCA suicides (65% v. 23%, P < 0.001). Demographic characteristics of antidepressant-related deaths in Maryland were similar to those of the entire USA. Possible explanations for the results obtained include the inherent lower lethality of fluoxetine compared to the TCAs, necessitating the use of additional means to complete the act of suicide; that physicians may have switched more impulsive, high risk patients to this new agent as it became available, thus creating a selection bias for more violence-prone individuals in the fluoxetine group; or that fluoxetine may be associated with induction of violence and/or suicidal ideation. Further research examining the possible association of these agents with violent acts is warranted.

Adolescent↗
PubMed1993

Measurement of heroin and its metabolites by isotope-dilution electron-impact mass spectrometry.

A solid-phase extraction procedure was developed for the isolation of heroin, 6-acetylmorphine, and morphine from blood, plasma, saliva, and urine with subsequent assay by gas chromatography/mass spectrometry. Aprotic solvents, mild elution conditions, and an enzyme inhibitor were used to ensure maximum analyte stability. Samples were extracted and the extract was divided into two equal portions. One portion was assayed directly for heroin; detector response was linear over a concentration range of 1.0 to 250 micrograms/L. The second part of the extract was reacted with N-methyl-bis-trifluoroacetamide and assayed for the trifluoroacetyl derivatives of 6-acetylmorphine and morphine; detector response was linear over a concentration range of 1.0 to 500 micrograms/L. The limit of sensitivity was 1.0 microgram/L for each analyte. Hydrolysis of heroin to 6-acetylmorphine during extraction and analysis was < 5%. The method can be used to corroborate heroin use and to study the pharmacological effects of heroin and its metabolites.

Body Fluids↗
PubMed1993

Interpretation of low postmortem concentrations of ethanol.

The interpretation of postmortem blood ethanol concentrations (BAC), especially those less than 0.05 g/dL can be complicated by postmortem ethanol formation. One method used by the toxicologist to respond to this possibility is to analyze multiple specimens for ethanol. Two useful specimens to analyze are vitreous humor and urine, because they are less susceptible to the putrefaction process. A negative vitreous humor and/or urine ethanol would suggest that the measured ethanol resulted from postmortem formation. Data were collected from the Office of the Chief Medical Examiner, State of Maryland and the Armed Forces Institute of Pathology on blood specimens with ethanol concentrations less than 0.05 g/dL to develop a reasonable threshold for interpretation in the absence of other specimens. A total of 381 cases with a BAC between 0.01 and 0.04 g/dL were studied over a 2 year period. Urine and vitreous humor specimens were tested where available. At a BAC of 0.01 g/dL, 54% of the cases were associated with a positive vitreous humor and/or urine ethanol concentration. This percentage increased to 63% when BAC equals 0.02 g/dL. Seventy-three percent and 92% of the cases had a positive alternate specimen if the BAC was 0.03 g/dL and 0.04 g/dL, respectively. In addition, 90% of the cases where both vitreous humor and urine were analyzed showed consistent results, that is both specimens were positive or negative. This suggests that in the absence of additional information, a BAC of 0.04 g/dL or higher probably resulted from ethanol consumption.

Alcohol Drinking↗
PubMed1992

Bupropion and alcohol fatal intoxication: case report.

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.

Adult↗
PubMed1990

Cocaine fatality: an unexplained blood concentration in a fatal overdose.

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.

Adult↗
PubMed1990

A fentanyl fatality involving midazolam.

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.

Adult↗
PubMed1990

Opiate analysis in cadaveric blowfly larvae as an indicator of narcotic intoxication.

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.

Animals↗
PubMed1990

Thiamylal: review of the literature and report of a suicide.

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.

Adult↗
PubMed1989

Phenol: tissue distribution in a fatality.

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.

Adult↗
PubMed1988

Incidence of cannabinoids in medical examiner urine specimens.

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.

Adult↗