Biomedical subjects

Y H Caplan

Publications and source records attributed to Y H Caplan.

71 records · Page 4Linked to original sources

PubMedDate not supplied

Two fatalities involving haloperidol.

Two cases are presented in which haloperidol was identified in postmortem toxicological analysis. One case was a suicidal overdose of the drug; the blood concentrations of haloperidol and reduced haloperidol were 1.9 and 1.4 mg/L, respectively. Bile, liver, and urine concentrations were 3.4 mg/L, 44 mg/Kg and 6.6 mg/L for haloperidol and 1.6 mg/L, 43 mg/Kg, and 5.7 mg/L for reduced haloperidol, respectively. The second case was believed to be a natural cardiac death with a blood haloperidol concentration of 0.6 mg/L. The distribution of haloperidol and reduced haloperidol in this case was bile, 0.4 and 0.5 mg/L; kidney, 0.7 and 2.3 mg/Kg; liver, 5.0 and 13 mg/Kg; and urine, 0.4 and 2.3 mg/L.

Adult↗

PubMedDate not supplied

Analysis of spleen specimens for carbon monoxide.

Crucial to the investigation of aircraft fatalities is the analysis of biological specimens for carbon monoxide (CO). In many cases, blood specimens are unavailable or unsuitable for analysis, and the testing of an alternate specimen for CO becomes necessary. Spleen specimens provide a rich source of red blood cells and hence can be a primary substitute for blood. To verify this, 40 paired blood and spleen specimens were analyzed for CO by using a gas chromatographic method. Ten specimens with a spleen CO saturation level (sat.) of less than 10% were associated with corresponding blood specimens with CO sat. less than 10%. Fifteen of the 18 spleen specimens with CO sat. greater than 29% were associated with blood specimens with greater than 48% sat. Results were inconclusive when the spleen CO sat. was between 10 and 29%. We concluded that spleen CO sat. can reflect blood CO sat. in certain situations, particularly when spleen CO sat. is high.

Carbon Monoxide↗

PubMedDate not supplied

Distribution of isoniazid in an overdose death.

A fatality due to the ingestion of isoniazid, a tuberculostatic agent, is presented. Isoniazid was extracted by a single step extraction procedure, derivatized with trifluoroacetic anhydride, and identified and quantified by gas chromatography/mass spectrometry (GC/MS). The distribution of isoniazid was as follows: heart blood 43 mg/L, subclavian blood 94 mg/L, urine 470 mg/L, bile 900 mg/L, liver 650 mg/Kg, kidney 110 mg/Kg, and stomach contents 4 mg.

Adolescent↗

PubMedDate not supplied

Concentration of cocaine and metabolites in plasma of humans following intravenous administration and smoking of cocaine.

Plasma was obtained from 10 human subjects at various intervals after administration of two rapid doses of cocaine, either intravenously or by smoking, and multiple doses by smoking and intravenously. The plasma was analyzed for COC and its metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME). Plasma concentrations of COC were found to be dose-dependent. For patients receiving two successive doses of COC intravenously (IV) or by smoking (SM), the average half-life of COC was found to be between 38 and 39 minutes, regardless of the dose or route of administration. Considerable interindividual variation was observed. Multiple doses of both SM and IV COC were administered to three patients in a manner consistent with COC abuse. The maximum COC concentration observed was 1.2 mg/L following a total administration of 316 mg of COC over 90 min. Analysis of BE and EME confirmed that BE is the principle metabolite of COC in blood. All COC was accounted for by BE. EME, when present, did not exceed 5% of the BE concentration.

Cocaine↗

PubMedDate not supplied

The role of ecgonine methyl ester in the interpretation of cocaine concentrations in postmortem blood.

A study of the metabolism of in vivo cocaine (COC) and the stability of in vitro COC suggests that the presence of benzoylecgonine (BE) in unpreserved blood arises from in vivo COC metabolism and that ecgonine methyl ester (EME) in unpreserved blood arises from in vitro COC hydrolysis. Postmortem cases positive for COC were studied to determine if molar concentrations of EME in unpreserved blood could be used to estimate the blood COC concentration at the time of death when added to the molar COC concentrations. COC was analyzed in 10 postmortem blood specimens between 1 and 8 days following death and again 10 to 70 days after further storage. The COC lost was accounted for by its hydrolysis to EME. Good correlation (r = 0.9677, p < 0.001) was observed when the blood COC concentrations in postmortem cases were compared to blood COC concentrations predicted by the addition of blood COC and EME concentrations; hence, analysis for EME and estimation of perimortem COC concentrations can assist in defining deaths associated with COC use.

Adolescent↗

PubMedDate not supplied

Detection of cocaine and its metabolites in human amniotic fluid.

The dramatic rise in maternal drug abuse and the incidence of positive drug findings during neonatal testing has increased the need for prenatal toxicological testing for drugs of abuse. Human amniotic fluid samples collected after 13-39 weeks of pregnancy were screened for cocaine metabolite (benzoylecgonine) by fluorescence polarization immunoassay (FPIA). All positive samples, as well as any accompanying maternal serum, were confirmed by gas chromatography/mass spectrometry (GC/MS) for cocaine and its metabolites. Five samples out of 450 were positive for cocaine, benzoylecgonine, and ecgonine methyl ester by GC/MS. In addition, one sample was also positive for cocaethylene. Two maternal serum samples were positive for benzoylecgonine and ecgonine methyl ester. The presence of cocaine, benzoylecgonine, ecgonine methyl ester, and cocaethylene in the amniotic fluid suggests that the fetus is exposed to cocaine and its metabolites through maternal circulation. The impact of this exposure on the health of the newborn is unknown.

Amniotic Fluid↗

PubMedDate not supplied

Serial capillary gas chromatography/Fourier transform infrared spectrometry/mass spectrometry (GC/IR/MS): qualitative and quantitative analysis of amphetamine, methamphetamine, and related analogues in human urine.

A method using serial capillary gas chromatography/Fourier transform infrared spectroscopy/mass spectrometry (GC/IR/MS) for the analysis of derivatized amphetamine, methamphetamine, and related analogues was developed. The GC/IR/MS was configured and optimized with a Hewlett-Packard (HP) 5890A gas chromatograph with a 12-m x 0.32-mm i.d. HP-5 capillary column serially interfaced through an HP 5965A infrared detector to an HP 5970 mass selective detector with a fused-silica 1.2-m x 0.10-mm i.d. column. Urine samples are extracted and derivatized as heptafluorobutyryl (HFBA) derivatives. For quantitation GC/MS in the selected ion monitoring (SIM) mode was used, with D,L-amphetamine-D5 as the internal standard. Gas chromatography/Fourier transform infrared spectrometry (GC/FT-IR) quantitation uses a selected wavelength chromatogram, spectral subtraction, double internal standard method using both D,L-amphetamine-D5 and 4-phenyl butylamine. Sensitivity for the combined GC/MS and GC/FT-IR system for amphetamine and methamphetamine shows limits of linearity of 100 to 5000 ng/mL, a limit of detection of 25 ng/mL, and a limit of quantitation of 98 ng/mL. The overall recovery for amphetamine and related analogues was greater than 85%. Precision studies for concentrations over the range of 200 to 1500 ng/mL showed coefficients of variations ranging from 2.8 to 13.0%. Correlation studies for quantitative GC/MS SIM and GC/FT-IR are greater than 0.98 for amphetamine, methamphetamine, and related analogues. Each analysis includes GC/MS SIM and GC/FT-IR quantitation, qualitative nonselective full spectra GC/FT-IR, and GC/MS scans of HFBA derivatives cross-referenced with an internal drug library, which provides high confidence and a means for the surveillance of amphetamine-like chemical analogues.

Amphetamine↗

PubMedDate not supplied

Disposition of heroin and its metabolites in heroin-related deaths.

Although many deaths occur annually from heroin intoxication, the presence of heroin has not been reported in postmortem tissues. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, extraction procedures were developed for the efficient recovery of heroin, 6-acetylmorphine, and morphine from postmortem tissue utilizing solid-phase extraction coupled with gas chromatography/mass spectrometry. From heroin-related deaths, 21 sets of blood and urine specimens were collected. The mode of death in these cases was categorized as rapid, delayed, or undetermined. Compared with delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine, and total opiates in blood; a higher ratio of free morphine concentrations to total opiate concentrations in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood of 6-acetylmorphine detection in blood; and lesser likelihood of heroin detection in urine. The study also included analysis of multiple tissue specimens from two subjects who died of heroin intoxication. Heroin was identified in urine and injection-site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen, and brain were substantially higher than in blood, liver, lung, and kidney. All specimens were positive for morphine. Heroin metabolites were detected in hair specimens. The identification of heroin and 6-acetylmorphine in biological tissues effectively established the presence of heroin in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information for the differential diagnosis of heroin-related deaths.

Drug Overdose↗

PubMedDate not supplied

Alternative specimens for workplace drug testing.

Recent advances in analytical techniques have enabled the detection of drugs and drug metabolites in alternative biological specimens for the purposes of workplace testing. A wide variety of specimens are available, each providing valuable information concerning prior or current drug use. The present focus is on oral fluid (saliva), hair, and sweat. An extensive evaluation by the Division of Workplace Programs of the Department of Health and Human Services is underway to determine the utility of these specimens in federally regulated programs. In future years, the testing of alternative specimens will expand our ability to understand the patterns of drug use and will become routine in all areas of forensic toxicology.

Hair↗

PubMedDate not supplied

A fatal overdose with colchicine.

A colchicine blood concentration 250 microgram/L was determined in a 39-year-old white female 2 hours following the ingestion of an oral overdose of the drug. At death, 40 hours following ingestion, no drug was detected. Colchicine was extracted from buffered blood using dichloromethane. The evaporated extract was redissolved in 0.1 N HCl and analyzed using a high performance liquid chromatograph equipped with an octadecylsilane reversed phase column.

Adult↗

PubMedDate not supplied

A method for the determination of therapeutic and toxic concentrations of tricyclic antidepressant drugs in post mortem fluids and tissues.

A sensitive and reliable procedure is presented for the measurement of the common tricyclic antidepressant (TCA) drugs in a variety of biological specimens at therapeutic as well as toxic concentrations. The method employs GC/NPD and a column packed with 3% OV-17 on Chromosorb W-HP. The pH of specimen extraction was optimized at 8.6, and 1-chlorobutane:ethyl ether (3:1) was found to be an efficient solvent for the primary extraction. Recoveries for all TCA drugs were at least 50% for each specimen. Linearity of extraction was observed over a range of therapeutic and toxic concentrations with a correlation coefficient greater than 0.99.

Antidepressive Agents, Tricyclic↗

PubMedDate not supplied

Blood and tissue concentrations of tricyclic antidepressant drugs in post mortem cases: literature survey and a study of forty deaths.

Blood, urine, heart, liver, and psoas muscle concentrations of tricyclic antidepressant (TCA) drugs and their N-desmethyl metabolites were determined in forty medical examiner cases. The cases were evaluated for the role played by the TCA drugs in the cause of death and compared to a literature survey of previously reported cases. The incidence of the various individual TCA drugs as a factor and the significance of the disposition of the drugs and their metabolites is included. Comparing TCA drug concentrations in the heart and skeletal muscle and considering the differences in perfusion to these organs, TCA drugs and metabolites showed an affinity for the cardiac over the skeletal muscle. The case results were correlated with experimental studies to suggest the relationships of blood concentrations with toxicity.

Adult↗

PubMedDate not supplied

The determination of amoxapine in human fatal overdoses.

Amoxapine, a recently introduced dibenzoxazepine, has been found effective in clinical studies for the treatment of various types of depression. Two amoxapine related deaths, a 53-year-old white male and a 21-year-old white female, have been investigated by this office. Both had been prescribed amoxapine for depression. Quantitation of amoxapine was by gas chromatography using a 3% OV-17 column with confirmation by ultraviolet spectrophotometry and thin layer chromatography. Blood amoxapine concentrations were found to be 18 mg/L in the first subject, and 6.7 mg/L in the second subject. These concentrations are many-fold higher than the therapeutic serum concentrations of up to 0.21 mg/L reported in a clinical study. These cases illustrate the potential lethality of amoxapine overdosage and the need for caution in prescribing amoxapine to patients with suicidal tendencies.

Amoxapine↗

PubMedDate not supplied

Therapeutic and toxic drug concentrations in post mortem blood: a six year study in the State of Maryland.

A six-year study of therapeutic and toxic drug concentrations in the blood from medical examiner's cases in the State of Maryland is reported. Statistical means, ranges, and number of cases are presented for three categories of cases; single drug deaths (53 drugs and 5 metabolites), multiple drug deaths (40 drugs and 5 drug metabolites), and non-drug related deaths (49 drugs and 5 metabolites). Results are compared to previous studies from the literature to facilitate, augment, and improve the understanding of the concentrations of drugs consistent with therapy or death.

Amitriptyline↗

PubMedDate not supplied

Urine cannabinoid analysis: an integrated multi-method approach.

The Enzyme Multiplied Immunoassay Technique (EMIT) Urine Cannabinoid Assay (Syva) was adapted for automated analysis on a centrifugal analyzer allowing for cost-effective, rapid, high-volume urine testing. Confirmation of positive EMIT results was accomplished by a modification of a recently published high performance liquid chromatographic (HPLC) technique for 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH). Further confirmation of the presence of THC-COOH was achieved by high efficiency thin layer chromatography (HETLC). The reported protocol was applied to urine samples obtained from an emergency toxicology population and a drug counseling population. Results indicated that specimens testing positive by all three methods suggest valid forensic evidence for the presence of THC-COOH.

Cannabinoids↗

PubMedDate not supplied

Liquid chromatographic determination of salicylate and methyl salicylate in blood and application to a postmortem case.

A liquid chromatographic method is presented for the quantitation of salicylate and methyl salicylate in blood. It employs an initial alkaline extraction to separate methyl salicylate from salicylate. Methyl salicylate is then hydrolyzed to salicylate, extracted under acidic conditions and chromatographed. This method was used in an attempt to identify methyl salicylate and salicylate in a postmortem case.

Chromatography, Liquid↗

PubMedDate not supplied

Chloral hydrate: unusually high concentrations in a fatal overdose.

A case in which chloral hydrate as a pure chemical rather than the prescribed drug caused the death of a 27-year-old white male is presented. Trichloroethanol was quantified in blood and tissues by electron capture gas chromatography. The blood trichloroethanol concentration found in this case (1700 mg/L) was higher than had been previously reported in the literature.

Adult↗