1/15. GHB. Club drug or confusing artifact?GHB can be produced either as a pre- or postmortem artifact. The authors describe two cases in which GHB was detected and discuss the problem of determining the role of GHB in each case. In both cases, NaF-preserved blood and urine were analyzed using gas chromatography. The first decedent, a known methamphetamine abuser, had GHB concentrations similar to those observed with subanesthetic doses (femoral blood, 159 microg/ml; urine, 1100 microg/ml). Myocardial fibrosis, in the pattern associated with stimulant abuse, was also evident. The second decedent had a normal heart but higher concentrations of GHB (femoral blood, 1.4 mg/ml; right heart, 1.1 mg/ml; urine, 6.0 mg/ml). Blood cocaine and MDMA levels were 420 and 730 ng/ml, respectively. Both decedents had been drinking and were in a postabsorptive state, with blood to vitreous ratios of less than 0.90. If NaF is not used as a preservative, GHB is produced as an artifact. Therefore, the mere demonstration of GHB does not prove causality or even necessarily that GHB was ingested. Blood and urine GHB concentrations in case 1 can be produced by a therapeutic dose of 100 mg, and myocardial fibrosis may have had more to do with the cause of death than GHB. The history in case 2 is consistent with the substantial GHB ingestion, but other drugs, including ethanol, were also detected. ethanol interferes with GHB metabolism, preventing GHB breakdown, raising blood concentrations, and making respiratory arrest more likely. Combined investigational, autopsy, and toxicology data suggest that GHB was the cause of death in case 2 but not case 1. Given the recent discovery that postmortem GHB production occurs even in stored antemortem blood samples (provided they were preserved with citrate) and the earlier observations that de novo GHB production in urine does not occur, it is unwise to draw any inferences about causality unless (1) blood and urine are both analyzed and found to be elevated; (2) blood is collected in NaF-containing tubes; and (3) a detailed case history is obtained.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
2/15. tissue distribution of olanzapine in a postmortem case.Olanzapine is a relatively new antipsychotic drug used in the united states for the treatment of schizophrenia. Since its release in the united states market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.- - - - - - - - - - ranking = 1.001449642341keywords = chromatography, extraction (Clic here for more details about this article) |
3/15. Redistribution of diltiazem in the early postmortem period.We determined tissue distribution of diltiazem after it was used to treat hypertension in two cases. The postmortem interval was 16 h in both cases. diltiazem was isolated using liquid-liquid extraction, and it was identified and quantitated using gas chromatography-mass spectrometry (GC-MS) and GC, respectively. In one case, diltiazem concentrations in the lungs and pulmonary vessel blood were 62-82 and 27-30 times higher than right femoral blood, respectively. Although blood was not obtained from the left cardiac chambers, aortic blood showed a 10-times higher level of diltiazem than right femoral venous blood. diltiazem concentration in blood in the right cardiac chambers was 3.6 times higher than that in right femoral venous blood. In another case, diltiazem concentrations in the lungs were 7.4-7.6 times higher than right femoral venous blood. Blood in the pulmonary arteries, pulmonary veins, left cardiac chambers, and aorta showed 2.0-3.1 times higher levels of diltiazem than right femoral venous blood. Blood in the right cardiac chambers displayed only 1.3 times higher level of diltiazem than right femoral venous blood. Our results strongly suggest that diltiazem accumulated in the lungs and was rapidly redistributed into pulmonary venous blood and then into the left cardiac chambers.- - - - - - - - - - ranking = 1.001449642341keywords = chromatography, extraction (Clic here for more details about this article) |
4/15. Utilizing the urinary 5-HTOL/5-HIAA ratio to determine ethanol origin in civil aviation accident victims.Specimens from fatal aviation accident victims are submitted to the FAA Civil Aerospace Medical Institute for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Care must be taken when interpreting a positive ethanol result due to the potential for postmortem ethanol formation. Several indicators of postmortem ethanol formation exist; however, none are completely reliable. The consumption of ethanol has been shown to alter the concentration of two major serotonin metabolites, 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindole-3-acetic acid (5-HIAA). While the 5-HTOL/5-HIAA ratio is normally very low, previous studies using living subjects have demonstrated that the urinary 5-HTOL/5-HIAA ratio is significantly elevated for 11-19 h after acute ethanol ingestion. Recently, our laboratory developed and validated an analytical method for the simultaneous determination of both 5-HTOL and 5-HIAA in forensic urine samples using a simple liquid/liquid extraction and LC/MS/MS and LC/MS/MS/MS. In this previous work a 15 pmol/nmol serotonin metabolite ratio cutoff was established in postmortem urine, below which it could be conclusively determined that no recent antemortem ethanol consumption had occurred. In the current study this newly validated analytical method was applied to five ethanol-positive aviation fatalities where the origin of the ethanol present could not previously be conclusively determined. In four of the five cases examined the detected ethanol was demonstrated to be present due to postmortem microbial formation, and not consumption, even though some indication of ethanol consumption may have been present.- - - - - - - - - - ranking = 0.0014496423409931keywords = extraction (Clic here for more details about this article) |
5/15. Comparative alcohol concentrations in blood and vitreous fluid with illustrative case studies.The toxicology Bureau of the new mexico Department of health performs drug and alcohol testing on approximately 2800 medical examiner cases each year across the entire state. Although blood is usually the preferred specimen for alcohol analysis, the importance of multiple specimen analysis in alcohol-related death investigation is well understood. Quantitative alcohol determination in a variety of postmortem specimens may provide important interpretive information. In a total of 322 consecutive cases, blood and vitreous alcohol concentrations were compared. No alcohol was detected in either specimen in only 27 of the cases. In the remaining 295 investigations, alcohol was detected in the vitreous fluid, blood, or both. Analysis of the data and presentation of case studies reinforce the need for multiple specimen analysis in alcohol-related death investigation. Postmortem blood and vitreous alcohol concentrations were compared in a series of 295 alcohol-positive cases. The vitreous alcohol concentration (VAC) exceeded the blood alcohol concentration (BAC) in 209 cases (71%). Blood alcohol concentrations exceeded vitreous concentrations in 81 cases (27%), and the concentrations were equivalent in 5 cases (2%). For the purpose of this study, samples that were negative in both specimens were excluded. In casework where the VAC > BAC, linear regression analysis indicated an R2 value of 0.958 (n = 209) and a VAC approximately 16% higher than the BAC. The VAC/BAC ratio was more variable at lower BACs (< 0.1 g/100 mL). The source of blood for this data set was predominantly femoral (n = 203), followed by heart (n = 5) and pleural cavity (n = 1). Although VAC/BAC ratios were more consistent at concentrations of 0.1 g/100 mL and above, the overall ratio ranged from 1.01 to 2.20. Of the 81 cases where BAC > VAC, a total of 24 cases indicated no vitreous alcohol. The range of blood alcohol concentrations among these cases was widely variable (0.01 to 0.30 g/100 mL). Unlike the VAC/BAC data set which consisted of 97% femoral blood, the source of blood in the BAC > VAC data set was slightly more variable. Of the 81 cases where BAC > VAC the blood source consisted of femoral (n = 68), heart (n = 8), pleural cavity (n = 2), carotid (n = 1), jugular (n = 1), and chest blood (n = 1). All analyses were conducted using dual-column gas chromatography with flame-ionization detection (GC-FID) with a reporting limit of 0.01 g/100 mL ethanol in postmortem samples. A series of case studies are used to demonstrate postmortem interpretive issues and the benefits associated with multiple specimen analysis. Cases include postmortem production of ethanol, rapid or unexpected death during the absorptive phase, and site-dependent differences following traumatic injury. Actual case studies involving other volatile organic compounds are also presented including isopropanol and acetone from endogenous and exogenous sources. Many of these cases studies highlight the difficulty associated with postmortem alcohol interpretation in the absence of multiple specimens or adequate case history.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
6/15. Postmortem tissue distribution of atomoxetine following fatal and nonfatal doses--three case reports.Atomoxetine (Strattera, Lilly) is a selective norepinephrine reuptake inhibitor (SNRI) prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children, adolescents, and adults. It is the first nonstimulant drug-therapy option for ADHD. Three case reports are presented in which atomoxetine was detected in two individuals who died from causes unrelated to the drug and a third from the intentional ingestion of atomoxetine and other drugs. In addition, a brief description of the pharmacokinetics and side effects of atomoxetine are given. Postmortem fluid and tissue concentrations of atomoxetine were as follows: aortic blood, <0.1-8.3 mg/L; femoral blood, 0.33-5.4 mg/L; vitreous humor, 0.1-0.96 mg/L; bile, 1.0-33 g/L; urine, <0.1 mg/L; liver, <0.44-29 mg/kg; and gastric contents, 0.0097-16.8 mg total. autopsy findings in the two cases in which death was not attributed to drug toxicity included arrhythmogenic right ventricular dysplasia and hypertrophic cardiomyopathy. The analytical method utilized was a modified basic drug, liquid-liquid procedure followed by gas chromatography/mass spectrometry and nitrogen phosphorous detection. Atomoxetine can be considered nontoxic at whole blood and liver concentrations below 1.3 mg/L and 5 mg/kg, respectively.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
7/15. Site-dependent postmortem changes in blood cocaine concentrations.When a forensic toxicologist interprets postmortem blood cocaine findings he usually must make assumptions regarding perimortem drug concentrations. In-vitro studies have shown that cocaine rapidly hydrolyzes in unpreserved blood, particularly at elevated temperatures. However, other studies have demonstrated site-dependent postmortem release of some drugs from tissue stores accompanied by increases in drug concentrations in the blood. This study was undertaken to investigate whether blood cocaine concentrations change in the body during the postmortem interval and, if so, to measure the direction and magnitude of the changes. In medical examiner cases in which scene investigation suggested that the decreased was a cocaine user, blood samples were collected as soon after death as possible. At autopsy, a second set of samples was collected. Analysis of paired samples by gas chromatography/mass spectrometry (GC/MS) revealed dramatic differences in the cocaine concentration. The magnitude and direction of the change appears to be site dependent. Usually, but not invariably, cocaine concentration in subclavian vein blood decreases while that in heart, aorta, and femoral vein blood increases during the interval between death and autopsy. The findings emphasize the danger inherent in attempting to estimate the concentration of cocaine in blood at the time of death from postmortem data.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
8/15. Postmortem pink teeth.A series of cases is reported in which pink teeth were observed during the postmortem period. Most cases were associated with decomposition in a moist environment. Experimental procedures led to the extraction of pink material from dentin and demonstration that hemoglobin and serum proteins were present. The pink-tooth phenomenon was duplicated in human teeth by instilling into the pulp chambers whole blood and blood with the red cells hemolyzed. The change was manifested in teeth of dogs after freezing, heating, and decomposition in a moist environment. The authors postulate that pink teeth occur as a result of breakdown of red blood cells in the pulp chamber of the tooth and diffusion of hemoglobin and other serum proteins into the dentin via the dential tubules. Histochemical studies show that the brown or gray material in some teeth subjected to postmortem aging is probably hemoglobin and serum proteins. Factors of age, vascularity of the pulp chamber, and postmortem conditions are discussed in relation to the postmortem development of pink teeth.- - - - - - - - - - ranking = 0.0014496423409931keywords = extraction (Clic here for more details about this article) |
9/15. Studies on the composition of gases in the post-mortem body: animal experiments and two autopsy cases.The composition of gases was measured in a cadaver, particularly in the stomach, using gas chromatography. High concentrations of carbon dioxide (CO2) and hydrogen (H2) and a low concentration of methane (CH4) were found. At an environmental temperature of 25 degrees C, the concentrations of CO2 and H2 were approximately 80% and 10%, respectively, at an advanced stage of putrefaction, while at an environmental temperature of 15 degrees C the concentrations were approximately 60% and 35%, respectively. These gases were not produced until the fourth day at 15 degrees C, but after that the volume of gases was greater than that produced at 25 degrees C, the cadaver becoming greatly enlarged. oxygen (O2) in air injected into a body disappeared during putrefaction. This study revealed that H2 was the main component of inflammable gas in a dead body. The mechanisms of production of the gases are also discussed.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
10/15. Postmortem clomipramine: therapeutic or toxic concentrations?Postmortem blood and liver concentrations of clomipramine were determined in ten cases by high performance liquid chromatography (HPLC). Blood concentrations ranged from 0.21 to 4.9 mg/L, and liver concentrations from 7.0 to 320 mg/kg. Two cases associated with clomipramine toxicity were clearly differentiated from other cases by the analysis of liver. The concentrations of clomipramine in these two cases were 3.3 and 1.8 mg/L in blood, and 280 and 320 mg/kg in liver. The liver concentrations were 10 to 30 fold greater in the deaths associated with drug toxicity compared with the other cases. One case, where cardiac blood was collected in place of femoral blood, showed a high blood concentration (4.9 mg/L), but an arguably therapeutic liver concentration (13 mg/kg). The analysis of femoral blood together with liver provides the best guide as to the significance of post-mortem clomipramine concentrations.- - - - - - - - - - ranking = 1keywords = chromatography (Clic here for more details about this article) |
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