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Synthetic cannabinoids emerged on the designer drug market in recent years due to their ability to produce cannabis-like effects without the risk of detection by traditional drug testing techniques such as immunoassay and gas chromatography--mass spectrometry. As government agencies work to schedule existing synthetic cannabinoids, new, unregulated and structurally diverse compounds continue to be developed and sold. Synthetic cannabinoids undergo extensive metabolic conversion. Consequently, both blood and urine specimens may play an important role in the forensic analysis of synthetic cannabinoids. It has been observed that structurally similar synthetic cannabinoids follow common metabolic pathways, which often produce metabolites with similar metabolic transformations. Presented are two validated quantitative methods for extracting and identifying 15 parent synthetic cannabinoids in blood, 17 synthetic cannabinoid metabolites in urine and the qualitative identification of 2 additional parent compounds. The linear range for most synthetic cannabinoid compounds monitored was 0.1-10 ng/mL with the limit of detection between 0.01 and 0.5 ng/mL. Selectivity, specificity, accuracy, precision, recovery and matrix effectwere also examined and determined to be acceptable for each compound. The validated methods were used to analyze a compilation of synthetic cannabinoid investigative cases where both blood and urine specimens were submitted. The study suggests a strong correlation between the metabolites detected in urine and the parent compounds found in blood. [ABSTRACT FROM AUTHOR]

The detection of new designer drugs is often a difficult issue in forensic urine drug testing as immunoassays are the primary screening methodology for drugs of abuse in many of these laboratories. Cross-reactivity of compounds with immunoassay kits can either aid or complicate the detection of a variety of drug and drug metabolites. For instance, emerging designer drugs that share structural similarities to amphetamines and phencyclidine (PCP) have the potential to cross-react with assays designed to detect these compounds. This study evaluates the cross-reactivity of five commercially available immunoassay reagent kits for 94 designer drugs on a Roche/Hitachi Modular P automated screening instrument. The compounds used in this study are grouped by structural class as follows: 2,5-dimethoxyamphetamines, 2C (2,5-dimethoxyphenethylamines), β-keto amphetamines, substituted amphetamines, piperazines, α-pyrrolidinopropiophenones, tryptamines and PCP analogs. A drug concentration of 100 µg/mL was used to determine cross-reactivity for each assay and resulted in the following positive rates: Microgenics DRI® Ecstasy enzyme assay (19%), Microgenics DRI® Phencyclidine enzyme assay (20%), Lin-Zhi Methamphetamine enzyme immunoassay (39%), Siemens/Syva® EMIT®II Plus Amphetamines assay (43%) and CEDIA® DAU Amphetamine/Ecstasy assay (57%). Of the 94 designer drugs tested, 14% produced a negative response for all five kits. No designer drug used in this study generated a positive result for all five immunoassay kits. [ABSTRACT FROM PUBLISHER]

A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT1B/1D receptors and is used for the treatment of migraines. The decedent was a 21-year-old white female found dead in bed by her spouse. No signs of physical trauma were observed and a large number of prescription medications were discovered at the scene. Toxicological analysis of the central blood revealed sumatriptan at a concentration of 1.03 mg/L. Following therapeutic dosing guidelines, sumatriptan concentrations do not exceed 0.095 mg/L. Sumatriptan was isolated by solid-phase extraction and analyzed using liquid chromatography–tandem mass spectrometry in multiple reaction monitoring mode. A tissue distribution study was completed with the following concentrations measured: 0.61 mg/L in femoral blood, 0.56 mg/L in iliac blood, 5.01 mg/L in urine, 0.51 mg/kg in liver, 3.66 mg/kg in kidney, 0.09 mg/kg in heart, 0.32 mg/kg in spleen, 0.01 mg/kg in brain, 15.99 mg/kg in lung and 78.54 mg/45 mL in the stomach contents. Carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan and hydroxyzine were also present in the blood at the following concentrations: 3.35, 2.36, 0.63, 0.19, 0.06, 0.55 and 0.16 mg/L. The medical examiner ruled the cause of death as acute mixed drug toxicity and the manner of death as accident. [ABSTRACT FROM AUTHOR]

In recent years, a class of new designer drugs commonly referred to as ‘bath salts’ have made their way to the illicit drug market. The most common drugs encountered are designer amphetamines and cathinones. Many analytical methods for analysis and identification of bath salts have been published, but there has been little reported on their impact on existing gas chromatography–mass spectrometry (GC–MS) amine confirmation methods. Due to structural similarities, the potential exists that designer amphetamines may interfere with methods used for analysis of sympathomimetic amines. Methiopropamine, 4-fluoroamphetamine, 4-fluoromethamphetamine (4-FMA) and 4-methylamphetamine were examined for potential interference with immunoassays and GC–MS confirmation analysis utilizing three derivatization procedures: R(-)-α-methoxy-α-trifluoromethylphenylacetyl chloride (R-MTPAC), heptafluorobutyric anhydride (HFBA) and chlorodifluoroacetic anhydride (ClF2AA). Significant cross-reactivity was observed with all the four compounds on the Syva Emit® II Plus Amphetamines and Roche KIMS Amphetamines II immunoassays. Laboratories utilizing GC–MS selected-ion-monitoring confirmation methods with R-MTPAC, HFBA or ClF2AA derivatives could experience potential chromatographic and mass spectral interferences from 4-fluroamphetamine, 4-FMA and methiopropamine in the form of ion ratio and quantitative failures. Careful ion selection, proper selectivity and specificity studies during method validation and rigid chromatographic and spectral acceptance criteria are required to assure the robustness and accuracy of GC–MS methods. [ABSTRACT FROM PUBLISHER]

A case is presented of a 19-year-old white male who was found dead in bed by a friend. While no anatomic cause of death was observed at autopsy, toxicological analysis of his blood identified AH-7921, a synthetic opioid. AH-7921 was isolated by liquid–liquid extraction into n-butyl chloride from alkalinized samples. Extracts were analyzed and quantified by gas chromatography mass spectrometry in selected ion monitoring mode. The heart blood had an AH-7921 concentration of 3.9 mg/L and the peripheral blood concentration was 9.1 mg/L. In addition to the blood, all submitted postmortem specimens including urine, liver, kidney, spleen, heart, lung, brain, bile and stomach content were quantified. The following concentrations of AH-7921 were reported: 6.0 mg/L in urine, 26 mg/kg in liver, 7.2 mg/kg in kidney, 8.0 mg/kg in spleen, 5.1 mg/kg in heart, 21 mg/kg in lung, 7.7 mg/kg in brain, 17 mg/L in bile and 120 mg/125 mL in the stomach content. The medical examiner reported that the cause of death was opioid intoxication and the manner of death was accident. [ABSTRACT FROM AUTHOR]

The article presents the postmortem case studies to determine the distribution of methylone. It mentions about a 19-year old male who was died due to cardiac arrest. It also mentions about a 21-year old female who died due to drowning while chasing by the police and a 35-year old female who was found dead on her bed with a cutting wound on neck and gunshot wound at the back of her head. The studies suggest that methylone and Methylenedioxypyrovalerone are more toxic when taken together.

The article presents a study which measures levetiracetam, topiramate, and hydroxycarbazepine in postmortem cases. The study uses acid or neutral drug screening process to quantify the drugs. Results show that the liver and kidney concentrations of the three drugs are on similar order of magnitude as the blood concentrations, however only the levetiracetam concentration in a single case showed a kidney or liver concentration greater than five times the blood concentration.

The article presents a study which investigates the overdose of extended-release oxymorphone hydrochloride tablets which resulted to death. It mentions the use of liquid chromatography, gas chromatography and mass spectrometry on the analysis of the concentrations of opiate in the blood and urine. Results show that the compounds temazepam, doxylamine and dextromethorphan are present in the urine samples.

The article presents a case study that evaluates the two cases of fatal overdoses of calcium channel blocker amlodipine. Postmortem samples were obtained and amlodipine was measured through liquid chromatography-atmospheric pressure photoionization-mass spectrometry. Results revealed that the heart blood concentrations for the two cases were 2.4 and 0.95 milligram per liter and such drug has been quantified in all other tissues.

The article presents a case of a 25-year-old white male who was found dead the morning after consuming herbal extracts containing β-carbolines and hallucinogenic tryptamines. No anatomic cause of death was found at autopsy. The medical examiner ruled that the cause of death was hallucinogenic amine intoxication, and the manner of death was undetermined.

Resveratrol, (3,5,4′-trihydoxystilbene) a compound found in grapes, mulberries, and peanuts, has antimycotic, antiviral, and beneficial cardiovascular and cancer preventive activities. It is being developed for several clinical indications. To evaluate the potential toxicity of resveratrol, rats were administered by gavage 0, 300, 1000, and 3000 mg trans-resveratrol per kilogram body weight per day for 4 weeks. Most of the adverse events occurred in the rats administered 3000 mg per kilogram body weight per day. These included increased clinical signs of toxicity; reduced final body weights and food consumption; elevated BUN, creatinine, alkaline phosphatase, alanine aminotransferase, total bilirubin, and albumin; reduced hemoglobin, hematocrit, and red cell counts; and increased white cell counts. Increases in kidney weights and clinically significant renal lesions, including an increased incidence and severity of nephropathy, were observed. Diffuse epithelial hyperplasia in the bladder was considered, equivocal and of limited biological significance. No histological effects on the liver were observed, despite the clinical chemistry changes and increased liver weights in the females. Effects seen in the group administered 1000 mg resveratrol per kilogram body weight per day included reduced body weight gain (females only) and elevated white blood cell count (males only). Plasma resveratrol concentrations in blood collected 1 h after dose administration during week 4 were dose related but were relatively low given the high dosage levels; conjugates were not measured. Under the conditions of this study, the no observed adverse effect level was 300 mg resveratrol per kilogram body weight per day in rats. [ABSTRACT FROM AUTHOR]

DFMO, an irreversible inhibitor of ornithine decarboxylase (ODC), is under development as a chemopreventive drug against cancers with pronounced proliferative phases. In support of human clinical trials, preclinical developmental toxicity studies were conducted in pregnant rats and rabbits. Rats were treated during GD 6-17, and fetuses were obtained by C-section on GD 20. Rabbits were treated during GD 7-20, and fetuses were obtained by C-section on GD 29. The dose range-finding study in rats (5/group at 0, 50, 125, 300, 800, or 1000 mg/kg/day) revealed maternal toxicity at doses ≥ 800 mg/kg/day (decreased body weights and food consumption) and developmental toxicity at doses ≥ 300 mg/kg/day (increased early resorptions and reduced fetal body weights). In the main study, rats (25/group) received 0, 30, 80 or 200 mg/kg/day. Developmental toxicity in the absence of maternal toxicity was observed at 200 mg/kg/day as significantly decreased fetal weights and increased incidence of litters with skeletal variations of 14th rudimentary rib, 14th full rib, and/or 27th presacral vertebrae. There were no treatment-related fetal skeletal malformations or external or visceral anomalies at any dose level. The dose range-finding study in rabbits (5/group at 0, 30, 60, 120, 240, or 500 mg/kg/day) revealed developmental toxicity at doses ≥ 60 mg/kg/day (increased resorptions and reduced fetal body weights) in the absence of maternal toxicity. In the main study, rabbits (20/group) received 0, 15, 45, or 135 mg/kg/day. Developmental toxicity in the absence of maternal toxicity was observed at 135 mg/kg/day as nonsignificantly increased early resorptions, decreased implantation sites, decreased viable fetuses, and reduced fetal weights. There were no external, visceral, or skeletal anomalies at any dose level. Thus, in the main developmental toxicity studies, DFMO produced developmental but not maternal toxicity at 200 and 125 mg/kg/day in rats and rabbits, respectively. Accordingly, in rats, the maternal no-observable-effect level (NOEL) was 200 mg/kg/day and the fetal NOEL was 80 mg/kg/day; while in rabbits the maternal NOEL was 135 mg/kg/day and the fetal NOEL was 45 mg/kg/day. These fetal NOELs are several-fold higher than the dose level currently used in Phase II and III clinical trials ( 13 mg/kg). [ABSTRACT FROM PUBLISHER]

One hundred and ninety-five patients undergoing abdominal surgical procedures completed a multicentre, randomized, open-label study comparing the safety and efficacy of cefmetazole and cefoxitin for the prevention of postoperative wound infection. Cefmetazole was administered iv in a single 2 g dose given within 90 min of the operation. Cefoxitin was administered in a single 2 g, similarly timed, preoperative dose and two additional doses given at 6 h intervals after surgery. For operations that exceeded 2–4 h duration an additional dose of each agent was administered. Patients undergoing colorectal operations received oral neomycin and erythromycin as bowel preparation. Colorectal operations were performed most frequently (49% of patients) followed by cholecystectomies (26%) and gastroduodenal procedures (21%). The operative site infection rate was 6–5% for cefmetazole and 7.7% for cefoxitin (P >0.05). Serious drug related adverse effects were not observed. This study demonstrates that administration of single-dose cefmetazole is as effective as a standard three dose regimen of cefoxitin for prophylaxis with abdominal operations. [ABSTRACT FROM PUBLISHER]

The safety and efficacy of intravenous cefmetazole for prophylaxis before abdominal operations were compared with those of intravenous cefoxitin in a randomized, prospective clinical study. Eighty-nine evaluable patients were enrolled. These patients underwent primarily clean/contaminated (56%) and contaminated (39%) operations. A total of three (3%) patients developed postoperative wound infections. Two patients (2%) developed non-life-threatening adverse drug reactions. There were no life-threatening adverse drug reactions. There were no significant differences between the cefmetazole and cefoxitin study groups. Cefmetazole appears to be as safe and as efficacious as cefoxitin antibiotic in prophylaxis for intra-abdominal operations. [ABSTRACT FROM PUBLISHER]

A modified stress model was studied to investigate the relationship between the stress response and drug metabolism in mice. Stress was induced in male CD-1 mice by a daily ip injection of hypertonic (1.5 M) saline for up to 3 days, whereas control animals received isotonic (0.15 M) saline. Two hours after receiving the saline injection on the first, second, or third day, animals were euthanized, and serum corticosterone (CORT) and liver aminopyrine N-demethylase (AD) and aniline hydroxylase (AH) activities were determined. To detect any effect of osmotic stimulation, a second control group was given 1.5 M saline as drinking water. There was no difference in CORT levels, AD activity, or AH activity between untreated animals and 0.15 M saline treatment. Intra peritoneal injection of 1.5 M saline markedly increased serum CORT concentrations compared to 0.15 M saline regardless of the duration of the treatment. Injection of 1.5 M saline also decreased both hepatic enzyme activities at each time point. Osmotic stimulation alone by hypertonic drinking water had no significant effect on CORT levels, AD activity, or AH activity. In another series of experiments, intact, sham-operated, and adrenalectomized mice were exposed to the stress model. Injected hypertonic saline decreased AD and AH activities in intact and sham-operated animals compared to isotonic saline-treated animals but both enzyme activities were reduced after adrenalectomy regardless of saline treatment used. In conclusion, a suitable model was established to study the interactions between the stress response and the hepatic drug metabolism in mice. [ABSTRACT FROM AUTHOR]

2-Mercaptobenzimidazole (2-MBI), used in rubber processing, is a suspect carcinogen structurally related to ethylene thiourea. The inhalation toxicity of 2-MBI was evaluated in male and female F344/N rats exposed 6 hr/day, 5 days/week to respirable aerosols generated by spray atomization of aqueous suspensions of the 2-MBI powder and subsequent drying of the resulting aerosols. Twelve exposures at target concentrations of 0, 6.3, 12.5, 25.0, 50.0, or 100 mg/m of 2-MBI produced a dose-related reduction in body weight gains, thyroid follicular cell hyperplasia, adrenal cortex fatty change, and pituitary atrophy. Sub-chronic exposures were conducted at target concentrations of 0, 3.1, 6.2, 12.5, 25.0, and 50.0 mg/m of 2-MBI. Rats at ≥25 mg/m displayed hunched posture, hypoactivity, and reduced body weight gain, with compound related mortality at the highest exposure level. Anemia; increased SGPT, SGOT, alkaline phosphatase, sorbitol dehydrogenase, BUN, and cholesterol; and reduced free fatty acid were seen in rats at ≥25 mg/m. Increased thyroid weight and thyroid follicular cell hyperplasia were noted in both sexes at ≥6.2 mg/m, with reduced triiodothyronine and thyroxine levels in both sexes at > 12.5 mg/m. Thyroid follicular cell hyperplasia was also seen in rats at 3.1 mg/m. Thymus weights were significantly reduced in both sexes at all exposure levels with liver weight increases at ≥6.2 mg/m. Exposure-related histopathologic changes included pituitary cytoplasmic vacuolization, adrenal cortex necrosis, lymphoid depletion, thymic atrophy, liver cell hypertrophy, renal mineralization and tubular atrophy, and hypocellularity of the bone marrow. [ABSTRACT FROM PUBLISHER]

The article provides information on the case of a 47-year-old man whose death was caused by an abuse on sevoflurane. The presence of sevoflurane was confirmed using a headspace gas chromatography-mass spectrometry. The concentration of the heart blood sevoflurane was 16 mg/L, and the concentration of the peripheral blood sevoflurane was 8.0 mg/L. When the heart blood was examined, no other drugs or other volatile substances were confirmed. Moreover, cardiac arrhythmia due to sevoflurane toxicity was the cause of his death as ruled out by the examiner.

Investigates hydroxycarbazepine distribution in three postmortem cases by researchers from Baltimore, Maryland. Detection of the active metabolite of the anticonvulsant oxacarbazepine in the biological specimens submitted for toxicological analysis; Use of gas chromatography-nitrogen-phosphorus for the detection of the compound; Assertion from the medical examiner that the hydroxycarbazepine was an incidental finding to the cause of death.

Presents an analysis of metformin in antemortem serum and postmortem specimens by a novel high-performance liquid chromatography (HPLC) method and application to an intoxication case. Performance characteristics of the metformin assay; Drugs tested and found not to interfere with the metformin assay; Elimination half-life of metformin.

Comments on the interpretation of analytical findings on urine samples generated by the laboratory by the forensic toxicologist. Role of the identified substances in the cause of death; Assessment of toxicity or impairment in living individuals; Correlation of impairment with drug concentrations.

A letter to the editor is presented in response to comments made to the author's article "A Fatal Intoxication Following the Ingestion of 5-Methoxy-N,N-Dimethyltryptamine in an Ayuhuasca Preparation."

The article presents a case study wherein the combination of 4-methymethcathinone (mephedrone) and heroin caused the accidental death of a 22-year-old male. The autopsy revealed needle marks in the lower legs and ankles of the decedent and detected morphine in the blood and urine samples using gas chromatography-mass spectrometry (GC-MS). The medical examiner determined the death was caused by accidental multiple-drug toxicity.

The article presents a study regarding the cyanide toxicology on fire victims' blood, corpse and stored tissue. According to the researchers, the modification of cyanide in tissues and blood is based on the first concentration of the compound when the victim died and how long the substance stayed in the corpse, stored and preserved.

The article examines the presence of 1-(3-trifluoromethylphenyl)-piperazine (TFMPP) and 1-benzylpiperazine (BZP) in urine samples using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) and gas chromatography-mass spectrometry (GC-MS). The BZP and TFMPP were detected through a full GC-MS scan of the seven U.S. service members' urine analysis specimen. Meanwhile, the LC-ESI-MS confirmed that in selected ion monitoring mode (SIM) yielded urinary concentrations ranging from 13.0 to 429.1 milligram/liter (mg/L) for BZP and 0.79 to 25.4 mg/L for TFMPP.

Discusses the increase number of admissions and deaths due to oxycodone abuse and overdose in the U.S. Identification of the drug in therapeutic drug-testing procedures; Result of routine gas chromatographic analysis of bile or urine; Evidence of known metabolic pathways of oxycodone in other species.

The article presents a study on the distribution of phencyclidine (PCP) into vitreous humor. It mentions that heart blood, subclavian blood and vitreous humor specimens from 26 PCP-positive postmortem cases were analyzed to evaluate the distribution of PCP in vitreous humor. It mentions that the specimens were analyzed by solid-phase extraction followed by gas chromatography-mass spectrometry. It declares that the results reveals that all positive blood specimens were associated with positive vitreous humor specimen, and on average, the blood PCP concentrations were greater than the vitreous humor PCP concentrations. It concludes that there were considerable variability between cases, which shows that the detection of PCP in postmortem cases' interpretative value is limited.

The article presents a case study of a 20-year-old decedent Caucasian male who was found dead under the bunk of his living quarters. It states that the decedent had used herbal supplements such as kratom to treat his insomnia. It mentions that fluorescence polarization immunoassay (FPIA) was utilized for the urinal screening to determine the existence of salicylate and acetaminophen. Furthermore, the presence of ethanol was not determined in blood of the decedent.

The article examines the content of Δ9-tetrahydrocannabinol (THC), the principal psychoactive compound in marijuana, in some commercially available hemp products marketed in health food stores as a good source of essential fatty acids. Methodology-wise, the THC obtained from alcoholic beverages, nutritional bars and oils were separated by a liquid-liquid or solid-liquid extraction. Based on the results, the researchers observed that products that were of aqueous base had much lower limits of detection.

The article presents a case study on tizanidine, a muscle relaxant agent found in the heart blood of the deceased 57-year old female in the U.S. Comprehensive toxicological analysis have identified ethanol, diazepam, and tizanidine in the heart blood. It is concluded that the cause of death was the combination of the ethanol and multiple drug intoxication, considering that 2.3 milligram per liter of tizanidine was obtained in the heart blood which exceeded normal the normal heart blood.

The article discusses a study designed to supplement previous attempts to establish an accurate range of normal endogenous gamma-hydroxybutyrate (GHB) concentrations in random antemortem urine samples. It aims to determine the effect of gender, race, age, medication, and select medical conditions on endogenous concentrations of GHB in urine and the proposed endogenous urinary GHB cutoff of 10 µg/mL.

Employs gas chromatography-mass spectrometry to monitor the excretion of total cannabinol in 4381 urine voids collected from seven participants through a controlled clinical study of multiple oral doses of cannabinol. Indication that terminal urinal elimination of cannabinol following oral administration was approximately two to three days.

The article focuses on the distribution of ether in two postmortem cases. Headspace gas chromatography-mass spectrometry in the selective ion monitoring mode was used to determine ether concentrations in the two cases. In the first case, the medical examiner ruled that the cause of death was asphyxia due to hanging. In case 2, the cause of death was asphyxia and the manner of death was suicide.

Reports on a case in which xylazine was identified in a suicide by hanging. Confirmation of the presence of xylazine by full scan electron ionization gas chromatography-mass spectrometry; Pharmacological analysis of the suicide case; Number of published cases of xylazine's involvement in human drug-related deaths and impairment.