Phencyclidine detection in nails.
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Biomedical subjects
Publications and source records attributed to Amanda J Jenkins.
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We report a case of a 75-year-old hypertensive, diabetic man who presented to the emergency room with symptoms and signs of nausea, acute intoxication, significant alteration in mental status with rapid neurologic deterioration, and blunt impact injuries sustained during a recent altercation with a 36-year-old female companion-caretaker. He denied a history of ethanol abuse or other recent toxic ingestion and had not been diagnosed with or treated for depression. Hospital laboratory tests revealed a metabolic acidosis and a negative urine toxicology screen. He was diagnosed with toxic encephalopathy with metabolic acidosis secondary to metformin. Despite treatments including hemodialysis, he expired after approximately 28 hours of hospitalization. A postmortem anatomic examination revealed recent blunt-impact injuries and cardiac and renal pathology. A subsequent histologic examination revealed the presence of calcium oxalate crystals in the kidneys and brain, in addition to cardiac and renal pathology. Comprehensive forensic toxicologic testing was performed on antemortem and postmortem samples and revealed lethal levels of ethylene glycol. The cause of death was as a result of acute intoxication by ethylene glycol with another condition of multiple blunt impacts to the head, trunk, and extremities. The manner of death was ruled as homicide. A trial by jury, involving the female companion-caretaker, resulted in her conviction, and she was sentenced to 23 years to life in prison. In this report, we present an unusual case of homicidal ethylene glycol intoxication in which legal proceedings have occurred.
Carbon monoxide (CO) poisoning as a cause of death is well documented in industrialized countries. The objective of this study was to compare demographic data in deaths due to accidents (in fires) and suicides in the same population between 1988 and 1998. Furthermore, the potential effect of a community wide education effort regarding safety in the home was assessed. Postmortem reports were reviewed for all deaths examined at the Office of the Cuyahoga County Coroner in Cleveland, OH, USA. During the study period, there were 209 accidental deaths due to fires in the home (6.5% of all accidents in the home) and 182 CO deaths by suicide (9.8% of all suicides). Demographic characteristics of the two groups differed: while males represented the majority of cases in both groups (55% of accidents, 70% suicides), race specific death rates were higher for whites than blacks (18/100,000 white, 3/100,000 black) in suicides compared with 29/100,000 deaths for blacks and 11/100,000 for whites in accidental cases. Fire deaths were prevalent in the young (0-9 years) and old (>60) whereas in the suicide group the age specific death rate was highest for those over 70 years. The majority of fire deaths occurred in the city of Cleveland but suicides were prevalent in the suburbs. More fire deaths occurred in December than any other month whereas more suicides occurred in April. In 1992, there was a community wide effort to provide free smoke detectors to residents in Cleveland. In 1992, there were 4.2/100,000 fire deaths in the city. This decreased to 0.6/100,000 in 1996, increased to 1.2/100,000 in 1997 followed by a decrease to 0.8/100,000 in 1998. This suggested that the program may have aided in decreasing these types of deaths. Deaths due to fires in the suburbs were <1/100,000 throughout the study period.
The ability to differentiate illicit from legitimate drug use in a drug-testing program would decrease costs by reducing the number of screening specimens requiring confirmation and also reduce the stigma attached to positive preliminary test results. Because many screening tests for drug detection use immunoassays, increasing the specificity of these tests has been a goal of manufacturers. In this study we evaluated the utility of one such assay, the Cedia heroin metabolite (6-acetylmorphine, 6-AM) assay to reliably detect heroin use. Specimens (N = 525) from a criminal justice drug-testing program were screened with this assay (cutoff concentration = 10 ng/mL 6-AM) and any positive samples were confirmed by gas chromatographic-mass spectrometric analysis (lower reporting limit for 6-AM = 5 ng/mL). The confirmation rate for the enzyme immunoassay (EIA) was 98% (517/525). Specimens contained 6-AM at concentrations ranging from 5 to 16,923 ng/mL (mean = 1251; median = 317). All confirmed specimens also contained morphine (range: 8-222,427 ng/mL; mean = 11,203 ; median = 4134). When challenged with standard drug solutions, the EIA correctly identified drug-free urine and produced positive results (lowest concentration, in ng/mL, that produced a positive result) with morphine at 10,000; oxycodone at 61,000; codeine at 60,000; hydromorphone at 10,000; hydrocodone at 60,000, 6-AM at 10, and pentazocine at 35,000 ng/mL. The Cedia heroin metabolite (6-AM) assay produced a high confirmation rate when challenged with urine specimens and therefore should be a useful tool in forensic toxicology. Potential users should be aware that high concentrations of other opioids (e.g., morphine, oxycodone) and structurally related compounds (e.g., pentazocine) may produce positive results.
The relationship between plasma and oral fluid concentrations of nicotine after infusion at varying times was investigated. Five healthy human volunteers were administered 0, 0.75, and 1.5 mg nicotine as 0.5-, 1.0-, 2.5-, and 5-minute infusions. Blood and oral fluid were collected before drug administration and for 4 hours thereafter. Nicotine concentrations were determined by HPLC using a limit of quantification of 1 ng/mL. Plasma nicotine concentrations were dose related. Peak plasma concentrations (mean+/-SD) at the 4 infusion times were 14.1+/-5.5, 11.8+/-5.3, 12.8+/-1.9, and 11.5+/-4.0 ng/mL (N=5) after the 0.75-mg dose and 26.3+/-11.7, 19.3+/-12.8, 24.54+/-10.4, and 19.02+/-6.5 ng/mL after the 1.5-mg dose. In general, the highest peak concentration occurred at the shortest infusion time at each dose. Peak nicotine oral fluid concentrations (mean+/-SD) at the 4 infusion times of 22.4+/-29.1, 22.64+/-29.9, 19.1+/-13.5, and 49.1+/-31.7 ng/mL (n=5) after the low dose and 35.8+/-21.1, 26.0+/-7.7, 33.3+/-28.8, and 104.0+/-68.9 ng/mL, after the 1.5 mg dose. The highest oral fluid concentration of nicotine occurred at the longest infusion time at each dose. Oral fluid/plasma were >1 for up to 60 minutes after the low dose and 120 minutes after the high dose. There was no correlation between plasma and oral fluid nicotine concentrations.
Previous studies have shown that up to 50% of adult drownings are related to the consumption of alcohol. Little information is available in the literature regarding the possible contribution of ethanol and other drugs to drownings. All records of deaths occurring in Cuyahoga County, Ohio, from 1994-2003, in which drowning was listed as the cause of death, were reviewed. Toxicology analysis was performed on cases where specimens were submitted. Review of the 187 cases showed that the majority (78%) of drowning deaths were ruled as accidents, 26 (14%) as suicide, 5 (3%) as homicide, and 11 (6%) as undetermined. Among the accidental deaths (n=141), 97 (69%) were negative for all drugs, including ethanol, and 30 cases (21%) were positive for ethanol only. Illicit drugs were detected in 4 of the cases (3%). In the suicides (n=26), 16 (62%) were negative for all drugs, including ethanol, and 7 cases (27%) were positive for ethanol only (mean blood alcohol concentration [BAC] 0.03 g/dL). Illicit drugs were detected in 3 of the cases (12%). Two of the 5 homicide cases (40%) were positive for ethanol. There were no cases in which the victim tested positive for illicit drugs. Of the 11 cases ruled as undetermined, 64% (n=7) were negative for all drugs, including ethanol. The remainder of the cases tested positive for ethanol only. There were no cases in which illicit drugs were detected. This study demonstrates that the majority of drowning deaths in Cuyahoga County, Ohio, were not drug related. Deaths in which drugs were detected were typically accidental deaths, with ethanol the most common drug detected.
Quetiapine is a new atypical antipsychotic that was approved in 1997 by the U.S. Food and Drug Administration for the treatment of schizophrenia. It possesses a high affinity for 5-HT2 receptors and a low affinity for D1 and D2 dopamine receptors. Because quetiapine has only been released recently to the U.S. market, little information exists regarding therapeutic, toxic, and lethal concentrations. This study reports the detection of quetiapine in 13 postmortem cases. Following a basic liquid-liquid extraction, quetiapine was identified and quantitated by capillary gas chromatography with nitrogen phosphorus detection. Confirmation was accomplished by full scan electron impact gas chromatography/mass spectrometry. Heart blood quetiapine concentrations ranged from 0.07 to 18.37 mg/L (N = 12, mean +/- SD = 3.42 +/- 5.67, median 0.62) and femoral blood concentrations ranged from 0.06 to 19.25 mg/L (N = 10. mean +/- SD = 3.89 +/- 6.12, median 0.81). The average heart blood/femoral blood ratio was 1.31 (range 0.55 to 2.57, N = 10). Urine, bile, and gastric contents were assayed in all cases in which they were submitted. In three cases, the cause of death was determined to be quetiapine toxicity. In these cases heart blood concentrations ranged from 0.72 to 18.37 mg/L (N = 3). These data may provide a basis for establishing levels associated with quetiapine toxicity as well as therapeutic concentrations in postmortem specimens.
A 40-year-old white male was found dead in bed in a group home for mentally ill adults. The decedent had been diagnosed a paranoid schizophrenic. An autopsy was performed at the Office of the Cuyahoga County Coroner in Cleveland, Ohio. Toxicological testing detected olanzapine and citalopram in post mortem specimens. Multiple fluids and tissues were assayed by liquid-liquid extraction followed by gas chromatography with nitrogen phosphorus detection, and qualitative confirmation by electron impact gas chromatography/mass spectrometry. Drug concentrations [olanzapine: citalopram; mg/L or mg/Kg] determined in this case are the highest reported to date involving these drugs- 1.38:3.35 heart blood, 1.11:1.65 femoral blood, 60.24:32.43 urine, 6.47:10:71 liver, and 38.36:49.16 lung, respectively. Drug concentrations in tissues were found to be the highest in lung for both drugs and lowest in the heart. Citalopram but not olanzapine was detected in bone. The cause of death was ruled acute intoxication by the combined effects of olanzapine and citalopram and the manner, accident.
It is well known that United States paper currency in general circulation is contaminated with trace amounts of illicit substances such as cocaine, heroin and marijuana. As is the case with cocaine, differentiating "background levels" of the various cannabinoid constituents of Cannabis sativa L., namely, Delta(9)-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD) contaminating currency found in the general circulation from currency associated with illegal drug activity is imperative if a legal nexus is to be established with the latter. We analyzed 165 randomly collected paper currency notes from 12 U.S. cities (N = 125) and 4 foreign countries (N = 40) for THC, CBD, CBN, 11-nor-9-carboxy-Delta(9)-tetrahydrocannabinol, and 11-hydroxy-Delta(9)-tetrahydrocannabinol. Uncirculated US 1 dollar notes were added as negative controls. Drug residues were washed from individual bills, extracted using a liquid-liquid extraction protocol, derivatized, and quantitated by gas chromatography-mass spectrometry by selected ion monitoring. For the US 1 dollar currency, THC was present in 1.6% (2 notes), CBN 10.31% (13 notes), CBD 1.6% (2 notes). The following concentrations were determined: 0.085 microg/bill and 0.146 microg/bill for THC; 0.014-0.774 microg/bill (mean 0.166 microg/bill) for CBN; and 0.032 microg/bill and 0.086 microg/bill for CBD. For the foreign currency (Colombia, Qatar, India, and New Zealand), THC and CBN were present in 22.5% (9 notes). The following concentration ranges were determined: THC 0.026-0.065 microg/bill (mean 0.049 microg/bill), CBN 0.061-0.197 microg/bill (mean 0.115 microg/bill). All of the positive THC and CBN were found in the New Zealand polypropylene notes. This study demonstrated that marijuana (cannabinoids) may contaminate both paper and plastic currency.
An unusual fatality secondary to oxycodone in a child is reported. A 2-year-old female child was conveyed to a local hospital after exhibiting signs of rubbing of the mouth and staggering. A hospital toxicological immunoassay screen for drugs of abuse and tricyclic antidepressants was performed on a urine sample and reported as negative. She was discharged and found unresponsive the next morning. She was conveyed to a second hospital in full cardiopulmonary arrest and despite resuscitative efforts, was pronounced dead upon arrival. An autopsy was performed and postmortem specimens were submitted and screened for drugs using mainly chromatographic techniques. Quantitation was achieved by gas chromatography with nitrogen phosphorus detection. Confirmation was performed by gas chromatography/mass spectrometry. Oxycodone was the only drug detected in the following concentrations: heart blood, 1.36 mg/L; gastric contents, 7.33 mg in 33 mL (222.34 mg/L); liver, 0.2 mg/kg; and urine, 47.23 mg/L (47,230 ng/mL). In addition, immunoassay testing of the urine was positive for the opiate class of drugs. This case report demonstrates an unusual cause of death in a young child with emphasis on potential limitation in hospital urine screening tests and the importance of complete forensic toxicological testing in all child deaths.
The relationship between blood cocaine concentrations and pharmacological effects is of both theoretical and practical interest. This study utilized a computer-assisted smoking device for the delivery of three active doses (10, 20, and 40 mg) of cocaine base to seven human volunteers. Doses were administered in an ascending dose design with random placement of placebo. Physiological, subjective, and performance measures were collected concurrently with blood samples. Mean peak plasma cocaine concentrations were achieved at 2 min after the 20-mg and 40-mg doses and at 5 min after the 10-mg dose. Maximal responses in systolic and diastolic blood pressure, "feel", "good" drug, and drug "liking" subjective effects were also achieved immediately after drug administration. Pupil diameter and heart rate increases demonstrated a modest counter-clockwise hysteresis in relation to plasma cocaine concentrations shortly after dosing. Systolic and diastolic blood pressure, heart rate, and some subjective and performance measures of drug effect demonstrated a biphasic response after smoked cocaine. Initial increases above baseline levels were followed by an apparent compensatory decrease below baseline levels at a later time after smoked cocaine. Despite evidence of hysteresis and biphasic responses for some measures, linear correlation was obtained between mean plasma cocaine concentrations and several pharmacological effects over a period of 4 h after dosing. Several subjective and cardiovascular measures returned to baseline levels in the presence of detectable concentrations of cocaine.
Postmortem fingernail and toenail specimens were utilized for the detection of cocaine analytes and opiates. Nail clippings were obtained from suspected overdoses and/or drug users. Nail clippings were washed with methanol and then solubilized in 0.1M potassium phosphate (pH 5.0). Analytes were isolated from the solubilized nails and methanolic washes by solid-phase or liquid-liquid extraction techniques. Quantitation was performed by gas chromatography-mass spectrometry. Clippings from each hand and foot were analyzed separately for comparison purposes. Concentrations of all the analytes were significantly higher in fingernails than in toenails. Cocaine analytes were detected in the nails of 15 cases with the following concentration ranges (ng/mg): cocaine (n = 15) 1.2-414.1; benzoylecgonine (n = 15) 1.4-170.3; ecgonine methyl ester (n = 14) 0.19-27.0; norcocaine (n = 12) 0.11-32.7; cocaethylene (n = 2) 0.08-2.93. Opiates were detected in 17 cases with the following concentration ranges (ng/mg): morphine (n = 15) 0.05-407.9; 6-acetylmorphine (n = 15) 0.04-504.0; codeine (n = 9) 0.06-8.84; hydromorphone (n = 4) 0.02-0.45. Oxycodone and hydrocodone were each detected in one case. The extent of drug incorporation due to external contamination was evaluated by comparing the differences in the amount of drugs detected in fingernails and toenails, along with the corresponding washes of those nails. These results demonstrate the usefulness of nails as postmortem specimens in detecting drugs of abuse.
Citalopram is a bicyclic phthalate compound approved in 1998 by the U.S. Food and Drug Administration for the treatment of depression. It is a highly selective serotonin reuptake inhibitor that appears to have little effect on noradrenaline or dopamine reuptake. Since this drug has only recently been released on the U.S. market, information regarding therapeutic, toxic, and lethal concentrations is sparse. This study reports the detection of citalopram in 22 postmortem cases. Citalopram was identified and quantitated by capillary column gas chromatography with nitrogen phosphorus detection after basic liquid-liquid extraction. Confirmation was achieved by full scan electron impact gas chromatography/mass spectrometry. In the 22 cases studied, heart blood citalopram concentrations ranged from 0.09 to 1.64 mg/L (n = 22, mean +/- SD = 0.51+/-0.43, median = 0.34); femoral blood concentrations ranged from 0.09 to 0.76 mg/L (n = 14, mean +/- SD = 0.34+/-0.23, median = 0.28); and urine concentrations ranged from 0.05 to 276.00 mg/L (n = 13). Liver was analyzed in three cases with citalopram concentrations ranging from 2.22 to 8.08 mg/kg. The average heart blood/femoral blood ratio was 1.26 (range 0.75 to 1.98, n = 14). In each case, the cause of death was not considered to be related to citalopram toxicity. These data may therefore provide a basis for establishing post mortem citalopram concentrations following therapeutic doses.
During a death investigation at the Office of the Cuyahoga County Coroner in Cleveland, OH, doxacurium became a drug of interest. The Coroner's Office enlisted the aid of the Federal Bureau of Investigation Laboratory for the doxacurium analysis. Following the request, a method for the extraction and qualitative analysis of the drug in biological fluids was developed. The procedure relies on a simple solid-phase extraction procedure followed by qualitative analysis with liquid chromatography-tandem mass spectrometry. During the development of the new analytical procedure, two breakdown products of doxacurium were detected. Structures for these breakdown products are proposed. This procedure was used to analyze heart blood, cerebrospinal fluid, and bile specimens from the decedent. Doxacurium and its breakdown products were identified in all three specimens.