The analysis of an intracerebral hematoma for drugs of abuse

Toxicological investigations were performed on an intracerebral hematoma, antemortem blood, and postmortem blood of an individual who was found unresponsive in his home. The hematoma was found to have ethanol at a concentration of 0.05% (w/v), and benzoylecgonine (a cocaine metabolite) was also confirmed at a concentration of 0.43 mg/L by specific analysis using gas chromatography/mass spectrometry (GC/MS). These results enabled the pathologist to record the cause of death as intracerebral hemorrhage due to acute cocaine intoxication.     

Deposition of cocaine in tissue after lethal and repeated sublethal administration to sheep

The deposition of cocaine in tissue after lethal administration to sheep was investigated. In addition, the presence of cocaine in tissue obtained from sheep treated for 30 days with a sublethal dose (2.4 mg/kg b.wt.) after 1-day, 1-week, or 1-month withdrawal was studied. The determination of cocaine was performed by radioimmunoassay. The concentrations measured represent the sum of cocaine and its metabolites. The presence of cocaine was also qualitatively proven by gas chromatography/mass spectrometry. After a lethal dose administration cocaine was found in all investigated organs. The highest concentrations were present in liver, bile, and kidney. In tissue obtained from the sheep treated daily with a sublethal dose and killed after 1-week withdrawal, the concentrations found were significantly lower. After 1-month withdrawal, cocaine was not to be discovered in tissue.     

Brain concentrations of cocaine and benzoylecgonine in fatal cases

Since cocaine in blood rapidly hydrolyzes to benzoylecgonine, cocaine concentrations determined in postmortem blood may not reflect the presence or concentration of cocaine in the body at the time of death. The interpretative value of the determination of cocaine and benzoylecgonine in brain tissue was investigated. Cocaine and benzoylecgonine were quantitated by coextraction and formation of the propyl derivative of benzoylecgonine followed by selected ion monitoring gas chromatography/mass spectrometry (GC/MS) using electron ion impact ionization. Cocaine and benzoylecgonine were found to be evenly distributed throughout the brain. Cocaine and benzoylecgonine concentrations were stable in frozen brain tissue (-4 degrees C) on reanalysis after 1 to 3 months of storage, and in refrigerated tissue (10 degrees C) after 30 days of storage. Blood, brain, and liver concentrations of cocaine and benzoylecgonine in 37 cocaine overdose cases and 46 cases in which cocaine was incidental to the cause of death were reviewed. The ratios of cocaine/benzoylecgonine in the toxic cases (brain mean 14.7 and blood mean 0.64) were clearly different from those found in the incidental cases (brain mean 0.87 and blood mean 0.27). The brain/blood ratios of cocaine and benzoylecgonine concentrations generally were characteristic of the time elapsed since cocaine dosing. In cocaine overdose cases, the mean ratio was 9.6 for cocaine and 0.36 for benzoylecgonine. These are within the range found in animal studies for brain/blood ratios of cocaine and benzoylecgonine 0.5 to 2 h after cocaine administration. In incidental cases, the brain/blood ratios were mean 2.5 for cocaine and 1.4 for benzoylecgonine.(ABSTRACT TRUNCATED AT 250 WORDS)     

A dextromoramide-related fatality

A 38-year-old man was found in his car suffering from a heart attack. Serum analysis by capillary gas chromatography and mass spectrometry confirmed the presence of dextromoramide (Palfium), methadone, and lidocaine. The serum concentrations at admission to the hospital were: 1.9 micrograms/mL of dextromoramide, 0.4 micrograms/mL of methadone, and 0.4 micrograms/mL of lidocaine. A serum alcohol analysis performed using headspace gas chromatography was negative.     

Studies on the stability and detection of cocaine, benzoylecgonine, and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid in whole blood using Abuscreen radioimmunoassay

A study was undertaken to assess the stability and the radioimmunoassay (RIA) detection of cocaine, benzoylecgonine (BZE), and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in whole blood while stored in 4 different kinds of blood collection tubes for up to 30 days at refrigeration and room temperatures. At various intervals, the tubes were sampled and analyzed using Abuscreen RIA. Also, semi-quantitative data derived from RIA analysis of forensic blood specimens were compared with quantitative data acquired using gas chromatography (GC) or GC/mass spectrometry (GC/MS) on the same specimens. RIA and chromatographic studies revealed that BZE and THC-COOH were stable in blood under all conditions studied. Cocaine, however, was found not to be stable in blood, especially when stored at room temperatures. Despite cocaine's instability in blood, RIA was able to detect the presence of cocaine and its breakdown products in blood under all conditions studied.     

The determination of cocaine and its major metabolite, benzoylecgonine, in postmortem fluids and tissues by computerized gas chromatography/mass spectrometry

An analytical procedure for the simultaneous determination of both cocaine and benzoylecgonine in postmortem fluid and tissue samples has been developed by using computerized gas chromatography/mass spectrometry and gas chromatography using a nitrogen/phosphorus (N/P) detector. Both methods are accurate and sensitive and allow the determination of tissue concentrations of cocaine and benzoylecgonine as low as 0.015 microgram/mL.     

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.     

Evidence on unusual way of cocaine smuggling: cocaine-polymethyl methacrylate (PMMA) solid solution--study of clandestine laboratory samples

An abandoned clandestine laboratory was seized in Slovenia. All confiscated exhibits were analysed in a forensic laboratory, where the following analytical methods were applied: capillary gas chromatography coupled with mass spectrometry (GC-MS) combined also by solid-phase micro extraction (SPME) and pyrolysis (Py) technique, Fourier transform infrared spectrometry (FTIR) and scanning electron microscopy with energy dispersive X-ray detector (SEM-EDX). The most interesting analytical findings can be summarised as follows: at the crime scene some plastic pieces, which contained cocaine dissolved (as solid solution) in polymethyl methacrylate-plexiglass (PMMA), were found. The highest cocaine concentration measured in the plastic sample was about 15% by weight. Two larger lumps of material (12 and 3 kg) were composed mainly of PMMA and CaCO3 and contained only 0.4 and 0.5% of cocaine, respectively. As for the low cocaine concentration, we assume that those two lumps of material represent discarded waste product--residue after the isolation of cocaine from plastic. Higher quantities of pure solvents (41 l) and solvent mixtures (87 l) were seized. We identified three types of pure solvents (acetone, gasoline and benzine) and two different types of solvent mixtures (benzine/acetone and gasoline/acetone). The total seized volume (87 l) of solvent mixtures holds approximately 395 g of solid residue formed mainly of PMMA and cocaine. Obviously solvent mixtures were used for isolation of cocaine from the plastic. Small quantities of relatively pure cocaine base were identified on different objects. There were two cotton sheets, most probably used for filtration. One sheet had traces of cocaine base (76% purity) on the surface, while cocaine in hydrochloride form (96%) was identified on the other sheet. GC-MS analyses of micro traces isolated from analytical balances showed the presence of cocaine and some common adulterants: phenacetine, lidocaine and procaine. A cocaine sample compressed in the shape of block was also seized. The above analytical findings inferred us to the conclusion that the illicit laboratory was used for the isolation of cocaine from PMMA resin. Further more, analyses confirm that not only isolation but also further manipulation of cocaine, i.e. adulteration/dilution, as well as the formation of cocaine blocks took place in the house. The information obtained through analyses also allowed us to make some hypotheses about possible multistage isolation procedure.     

Cocaine in decomposed human remains.

From March 1988 through March 1990, at the Philadelphia Medical Examiner's Office toxicology laboratory, samples from 77 decomposed human bodies were tested for the presence of cocaine, employing gas chromatography/mass spectrometry (GC-MS). The material analyzed included decomposed soft tissue, bloody decomposition fluid, mummified tissue, maggots, and beetle feces. Twenty-two cases (28.6%) were positive for cocaine, many of these cases in states of advanced decomposition. These findings indicate the usefulness of testing decomposed tissue for cocaine in all cases where its presence is suspected. This is contrary to what might be expected, since cocaine is generally labile and rapidly broken down by both enzymatic and nonenzymatic mechanisms.     

The Quantitation of Cocaine on U.S. Currency: Survey and Significance of the Levels of Contamination

It has long been suspected that the illicit distribution of cocaine in the United States has led to a large‐scale contamination of the currency supply. To investigate the extent of contamination, 418 currency samples (4174 bills) were collected from 90 locations around the United States from 1993 to 2009. The extent of their cocaine contamination was quantitated via gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. The level of cocaine contamination was determined to average 2.34 ng/bill across all denominations ($1, $5, $10, $20, $50, and $100). Levels of cocaine contamination on currency submitted to the Federal Bureau of Investigation Laboratory in criminal cases over the 1993–2001 timeframe had significantly higher contamination than currency in general circulation. A mathematical model was developed based on the background survey that indicates the likelihood of drawing a bill in specific concentration ranges. For example, there is a 0.8349 likelihood that random bill will have contamination less than 20 ng.     

Death of a 10‐Month‐Old Boy After Exposure to Ethylmorphine

Abstract: Ethylmorphine, an opiate that is partially metabolized to morphine, is a common ingredient in antitussive preparations. We present a case where a 10‐month‐old boy was administered ethylmorphine in the evening and found dead in bed the following morning. Postmortem toxicological analyses of heart blood by gas chromatography‐mass spectrometry and liquid chromatography‐mass spectrometry revealed the presence of ethylmorphine and morphine at concentrations of 0.17 μM (0.054 mg/L) and 0.090 μM (0.026 mg/L), respectively. CYP2D6 genotyping showed that the deceased had an extensive metabolizer genotype, signifying a “normal” capacity for metabolizing ethylmorphine to morphine. The autopsy report concluded that death was caused by a combination of opiate‐induced sedation and weakening of respiratory drive, a respiratory infection, and a sleeping position that could have impeded breathing. This is the first case report where the death of an infant has been linked to ethylmorphine ingestion.     

Determination of cocaine in human hair by gas chromatography/mass spectrometry

A qualitative method for the determination of cocaine alone without its metabolites in human hair by gas chromatography/mass spectrometry (GC/MS) was developed. The assay used helium as carrier gas, a 30-m bonded phase fused silica OV-1 capillary column, and solid injection at 290 degrees C evaporator temperature. The cocaine concentrations in hair were determined also by radioimmunoassay (RIA). The values obtained are the sum of cocaine and its metabolites. Both GC/MS and RIA meet the requirements for the determination of drug abuse by two different methods in forensic science.     

Fatal bromethalin poisoning

Bromethalin is a neurotoxin found in some rodenticides. A delusional 21-year-old male presented to a hospital with altered mental status the day after ingesting a bromethalin-based rodenticide. He died 7 days after his self-reported exposure to c. 17 mg bromethalin (equivalent to 0.33 mg bromethalin/kg). His clinicopathologic course was characterized by altered mental status, obtundation, increased cerebrospinal fluid pressure, cerebral edema, death, and diffuse histologic vacuolization of the white matter in the central nervous system seen on microscopic examination at autopsy. The presence of a demethylated form of bromethalin in the patient's liver and brain was confirmed by gas chromatography with mass spectrometry. Clinical signs and lesions observed in this patient are similar to those seen in animals poisoned with bromethalin. This case illustrates the potential for bromethalin ingestion to result in fatal human poisoning.     

Acute intoxication with orphenadrine and clozapine.

This report describes a fatal intoxication with two different drugs: clozapine and orphenadrine. A 38-year-old man was found dead in the bedroom of his residence. Near the body were found various empty pharmaceutical boxes, employed in schizophrenic therapy, two of them containing clozapine and orphenadrine. High concentrations of clozapine and orphenadrine detected in blood, urine and gastric content were related to death. These compounds were identified and quantitated by liquid-liquid extraction followed by gas chromatographic/mass spectrometry (GC/MS) analysis.     

Fatal intoxication involving 2-methyl AP-237

Novel synthetic opioids contribute considerably to the opioid epidemic, especially with the frequent emergence of structurally similar compounds. This case report describes a fatal intoxication involving 2-methyl AP-237. A 54-year-old Caucasian male was found deceased from an apparent drug overdose. A plastic container labeled “2MAP” and a cut straw were found in the decedent's backpack at the scene. A white substance found in the container tested positive for fentanyl by field testing. According to his medical history, the decedent was treated for a drug overdose 3 years prior to his death. With no diagnostic findings at autopsy, the case was submitted for toxicological analysis. An unknown substance was detected in peripheral blood and urine using gas chromatography with nitrogen phosphorous detection (GC-NPD). Further testing was conducted using gas chromatography–mass spectrometry (GC–MS) and liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS) which confirmed the presence of 2-methyl AP-237 and potential metabolites in blood and urine. Quantitation by GC-NPD revealed concentrations of 2-methyl AP-237 in blood and urine at 480 ng/mL and 4200 ng/mL, respectively. The toxicological analysis also identified and quantitated alprazolam in the blood at 55 ng/mL. Additionally, the metabolism of 2-methyl AP-237 was investigated and three hydroxylated metabolites were identified in peripheral blood and urine. Limited literature is available for the detection and quantitation of 2-methyl AP-237 in postmortem specimens. Given the toxicological findings with unremarkable autopsy findings, this case is an example of a fatal intoxication involving 2-methyl AP-237.     

Simultaneous identification and δ¹³C classification of drugs using GC with concurrent single quadrupole and isotope ratio mass spectrometers

In this study, δ13C values of six cocaine samples were identified and classified using a single quadrupole mass spectrometer and an isotope ratio mass spectrometry (IRMS) as simultaneous gas chromatography detectors. Our instrument modification is simple to use and is useful (i) when the sample is of limited size or can only be injected once, (ii) to help identify peaks in a complicated IRMS chromatogram, and (iii) to help differentiate very simple systems when impurity profiling is not possible. The EI-MS confirmed the identity of cocaine in each sample. The IRMS data distinguished 12 of the 15 possible pair-wise comparisons at the 95% CL. Three samples could not be differentiated by their δ13C ratios for cocaine. ANOVA demonstrated that the measurement variance was consistently larger than the sample variance. As the δ13C values clearly show, this technique enables the exclusion of a potential common source even when two samples have otherwise identical chemical and physical properties.     

Determination of butane in respiratory gases by means of GC/MS and GC/MS-MS

Butane is inhaled in order to achieve a pleasurable state of intoxication. An overdose can lead to death. In two deaths from our own investigation material the circumstances were suspicious for the inhalation of liquid gas, and the presence of butane should be demonstrated in the respiratory gases. For detection, a method of ion trap gas chromatography/mass spectrometry (GC/MS) and tandem-mass spectrometry (GC/MS-MS) was developed, whereby the gas samples from the lung tissue were directly injected into the GC. The GC/MS tests revealed the presence of butane. Moreover, it was found that during the MS-MS tests reaction products appeared which had formed in the ion trap. Systematic investigations of these reaction products showed that these appeared regularly and could be used as additional backup for the proof of butane. Thus phenomena in the ion trap were used which would not have been expected to occur in normal mass spectrometry or tandem-MS and had not been described in the forensic literature so far. The detected amount of butane could be quantified by means of serial dilutions with nitrogen and room air. The described method shows that small molecules or gases can be demonstrated with the ion trap mass spectrometer.     

Coca paste: chemical analysis and smoking experiments

Several samples of Colombian and a sample of Peruvian coca paste were subjected to chemical analysis to ascertain the complexity of these products. A neutral and acid fraction and a basic fraction were analyzed by gas chromatography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS). The basic fraction was also analyzed as its trimethylsilyl (TMS) derivative. Several gasoline residue components were identified in the neutral fraction. In addition to cocaine (greater than 60% in all cases), other alkaloids were identified. Lead and manganese analyses were carried out on these samples. While all the samples contained no lead (less than 45 ppm), most of the Colombian samples contained significant amounts of manganese (greater than 5%). Preliminary smoking experiments with a Colombian coca paste sample indicated that it behaves more like free cocaine than like a cocaine sulfate salt.     

Identification and quantification of phenobarbital in a mummified body 10 years after death

Abstract: This article reports the determination of phenobarbital in the mummified body of a 56‐year‐old man found completely mummified 10 years after his death. When alive, he was being treated for epilepsy with phenobarbital, and the recent analyses, performed with both immunochemical techniques and gas chromatography with mass spectrometry (GC‐MS), have revealed the presence of this substance in various tissues: the mean content of barbiturate in the mummified liver tissue was 93 μg/g, 216 μg/g in the heart, 17 μg/g in the lungs, 12 μg/g in muscles, and 31 μg/g in the skin. Preliminary screening tests with immunochemical techniques to evaluate the presence of other drugs were also performed. The sample resulted negative for all substances tested. Phenobarbital can be identified and quantified thanks to its excellent chemical stability and a hypothesis of what the concentrations in the fresh tissue could have been has also been reported.     

Changes in illicit cocaine hydrochloride processing identified and revealed through multivariate analysis of cocaine signature data

For nearly 30 years, the methods utilized in illicit cocaine hydrochloride production have remained relatively consistent. Cocaine hydrochloride is typically produced one kilogram at a time. As a result, each individual kilogram is unique and distinct from other kilograms in any particular seizure based on the total alkaloid profile, occluded solvent profile, and isotopic signature. Additionally, multi-kilogram cocaine seizures are often comprised of cocaine from several different coca growing regions. There has been a documented shift in this type of processing based on the recent analysis of a large cocaine seizure in the Eastern Pacific. Signature analyses of samples from 21 kg randomly selected from a 517 kg seizure were virtually identical. Triplicate analyses of each sample via gas chromatography with flame ionization detection, static headspace gas chromatography mass spectrometry, and isotope ratio mass spectrometry were completed. An initial outlier evaluation of the data and an in-depth univariate analysis indicated there was no statistically significant difference among the 21 samples at the 95% confidence interval. Principal components analysis did reveal consistent minor deviations between the samples and known authentic data from the Nariño coca growing region of Colombia. These deviations were only observed on the latter principal components and could be explained by differences in solvent selection during cocaine hydrochloride processing. Chemical analyses in addition to a thorough statistical evaluation suggest a shift in the traditional small-batch method of cocaine processing to a multi-kilogram, high throughput approach.