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BACKGROUND Coronavirus disease 2019 (COVID-19) has led to over 500 million cases and 6.2 million deaths around the world. Low and middle income countries (LMICs) like Armenia have faced unique infrastructure, financial, and capacity challenges that in many cases resulted in worse outcomes. Healthcare facilities across Armenia experienced a shortage of resources including hospital beds and oxygen which was further exacerbated by the war with neighboring Azerbaijan. Without a framework for home-based care, healthcare facilities were severely strained by COVID-19 patients who had prolonged oxygen requirements but were otherwise clinically stable. OBJECTIVE This paper describes our approach to establishing an international collaboration to develop a web application to support home monitoring for patients with COVID-19 with persistent oxygen requirement. METHODS The app was developed using a rapid, coordinated, and collaborative approach involving an international group of clinicians, developers, and collaborators. Health screening, monitoring, and discharge forms were developed into a lightweight OpenMRS web-app and customized for the local Armenian context. RESULTS The software was designed and developed over 2 months using human centered design and agile sprints. Once live, 5,022 patient records were created for 439 unique patients. CONCLUSIONS This project suggests a promising framework for designing and implementing remote monitoring programs in LMICs despite pandemic and geopolitical challenges.

Background A critical decrease in the number of healthcare providers in developing countries is one of the major burdens to healthcare access in these countries. Many factors contribute to the lack of healthcare providers, including low doctor-to-population ratio, emigration of doctors to other countries, long travel distances to hospitals, increasing cost of healthcare, and concentration of doctors in urban cities. Several measures have been taken by both governmental and nongovernmental organizations in these countries to mitigate this crisis with varying outcomes. In this study, we investigate the use of technology in the form of telemedicine in a developing country. We evaluate patient predisposition to the use of telemedicine, their experience, and some challenges involved in the use of telemedicine in this setting. Methodology We set up an electronic medical record system, OpenMRS, and added telemedicine modules to the system. Then, we recruited doctors and gave them privileges on OpenMRS after carefully vetting their credentials. Finally, we set up a website through which patients could request telemedicine consultations. We registered a telephone number in Nigeria so that patients could also request consultations via SMS. Consult requests were then entered into OpenMRS. Doctors logged in periodically and checked for patients awaiting consults. They called patients, diagnosed them, requested further diagnostics, and/or sent prescriptions to patients via SMS directly from OpenMRS. Results Data were collected over the first year of telemedicine service in Nigeria. These data were then analyzed to understand the effectiveness, patient experience, cost efficiency, and general utilization of this service. In the first year, there were 510 new patient registrations and 572 total consultations. Patient age ranged from less than one year to 77 years, with a median of 29 years. Among the users of the service, 51.8% (264) were female. For consult requests, 52.2% of requests were via the web, and others were via SMS requests. There were over 50 reviews of the service on the website and social media, and 95% of users reported a positive experience. Conclusions From preliminary data, telemedicine can potentially be a good adjunct to help doctors reach their patients, especially in rural areas where there is an immense shortage of healthcare professions. Although most patients reported a positive experience, further investigations are needed to validate our experience.

After all of the analytic data have been accumulated, the final step in the toxicologic process is to assess the meaning of the results. In suspected drug intoxications, one must determine if the amount of toxicant or toxicants present in the appropriate specimens is consistent with producing lethality. This decision ultimately must be made by the medical examiner or coroner, who must also consider the history, scene investigation, and gross and microscopic autopsy findings in reaching this decision. Once the cause of death has been determined, the manner of death needs to be decided. This can produce another group of questions to be addressed by the toxicologist. Items such as route of administration, acute versus chronic dose, and consistency between drug concentrations and behavioral effects may be critical factors in assessing the manner of death. These questions may arise even if the cause of death is ruled not to be drug related.

Central nervous system (CNS) depressants remain a frequently encountered class of drugs in forensic toxicology. The most commonly encountered group, the benzodiazepines are discussed in Chap. 20. The oldest group of CNS depressants, the barbiturates, are still used therapeutically, principally as anesthetic agents and anticonvulsants. Barbiturates are classified based on their chemical structure, duration of action, and pharmacological properties. Gamma-hydroxybutyric acid (GHB) is a simple hydroxylated, short-chain fatty acid with a very short duration of action. However, its detection in biological specimens is complicated by the fact that it is also produced endogenously from the metabolism of the neurotransmitter gamma-aminobutyric acid (GABA) and is produced in postmortem blood specimens. Zolpidem, zopiclone, and zaleplon, collectively known as “z-drugs,” all interact with the GABA receptor in different ways to produce their CNS depressant effects. Some of the newer CNS depressants that are used to manage sleep disorders include melatonin agonists such as ramelteon and tasimelteon, and dual orexin receptor antagonists such as suvorexant. Other sedative-hypnotics, muscle relaxants, and drugs with CNS depressant activity are also discussed.

Drug stability is an important consideration that is sometimes overlooked. However, changes in drug concentration can occur after specimen collection, during storage, shipping, transport, and evidence handling. Although environmental conditions, such as temperature and exposure to light, can play an important role, drug stability is analyte dependent and is largely determined by physicochemical properties of the molecule. The stability of common drug classes in biological matrices is reviewed within the context of proper specimen preservation and storage. Differences between antemortem and postmortem specimens are also addressed.

Carbon monoxide (CO) poisoning is the leading cause of both accidental and intentional poisoning deaths in the United States. Carbon monoxide produces its toxic effects primarily by reducing the oxygen availability to tissues (anoxic anoxia) in two ways: CO binding to hemoglobin (Hb) reduces the amount of Hb available to carry oxygen to tissues and prevents the release of some of the oxygen from Hb binding sites at the low oxygen tension present in the tissues (leftward shift in the oxygen-Hb dissociation curve). The signs and symptoms of CO intoxication are relatively nonspecific; treatment of CO poisoning is primarily supportive. Evaluation of the extent of CO exposure is based on a determination of the percentage of Hb bound with CO (%COHb) in the blood. Fatalities due to CO exposure are typically characterized by %COHb >50%. The presence of a bright cherry-red coloration of the blood, fingernails, mucous membranes, and skin may indicate CO poisoning. Cyanide is a fast-acting, lethal poison, with death occurring within minutes after inhalation and more slowly following oral ingestion. Cyanide inhibits the electron transport process of cellular respiration at the cytochrome c oxidase step, binding to the heme ion of cytochrome c oxidase. Hydrogen cyanide (HCN) is more rapidly absorbed than salts of cyanide. Detoxification of cyanide to thiocyanate occurs via two enzyme systems: rhodanese and beta-mercaptopyruvate-cyanide sulfurtransferase. The onset of symptoms in cyanide poisoning is dependent on the type of exposure; HCN vapor acts more quickly than cyanide salts. The signs and symptoms of cyanide poisoning are relatively nonspecific, with rapid onset of coma, metabolic acidosis, and symptoms of anoxia without cyanosis as noteworthy indicators. Cyanide deaths have occurred from both accidental and intentional exposure. The findings at autopsy are generally nonspecific. Blood cyanide concentrations of 2–3 mg/L are consistent with death in the absence of other findings.

In an effort to identify new antidiabetic agents, we have discovered a novel family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine analogues which are inhibitors of human glycogen synthase kinase 3 (GSK3). We developed efficient synthetic routes to explore a wide variety of substitution patterns and convergently access a diverse array of analogues. Compound 1 (CHIR-911, CT-99021, or CHIR-73911) emerged from an exploration of heterocycles at the C-5 position, phenyl groups at C-4, and a variety of differently substituted linker and aminopyridine moieties attached at the C-2 position. These compounds exhibited GSK3 IC50s in the low nanomolar range and excellent selectivity. They activate glycogen synthase in insulin receptor-expressing CHO-IR cells and primary rat hepatocytes. Evaluation of lead compounds 1 and 2 (CHIR-611 or CT-98014) in rodent models of type 2 diabetes revealed that single oral doses lowered hyperglycemia within 60 min, enhanced insulin-stimulated glucose transp...

The Substance Abuse and Mental Health Services Administration (SAMHSA, an agency under the US Department of Health and Human Services) drug testing program was initiated in 1988 to include the primary drugs of abuse during that time period: amphetamine/methamphetamine, cocaine, marijuana, phencyclidine (PCP), and morphine/codeine. In subsequent revisions, other analytes, including 6-acetylmorphine (6-AM), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA), have been added to the testing panel. Revisions proposed in 2015 add oxycodone, oxymorphone, hydrocodone, and hydromorphone, which will be discussed in further detail under non-SAMHSA drug section. For workplace drug testing, initial step is immunoassay screening using an Food and Drug Administration (FDA) approved immunoassay followed by confirmation using an alternative method preferably gas chromatography/mass spectrometry (GC/MS) or liquid chromatography combined with mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS). Some drug metabolites are excreted in urine in conjugated form so hydrolysis of urine prior to extraction is useful in liberating free drugs. One major advantage of LC-MS/MS is that unlike GC/MS where derivatization is needed for several drugs, for LC-MS/MS most drugs can be analyzed without derivatization.

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 effect were 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.

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.

A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT(1B/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.

Caffeine, 1,3,7-trimethylxanthine, is the most widely consumed legal stimulant. The most potent form is over the counter oral tablets. The estimated average daily adult caffeine consumption is 300 mg. Rarely, serious toxicities such as seizure and cardiac arrhythmias have caused death. Caffeine concentrations of 80 mg/L are considered lethal. Cases investigated over 10 years by the Office of the Chief Medical Examiner for the State of Maryland (OCME) whose cause of death was solely or in combination due to caffeine intoxication were reviewed. A total of eight adult cases were identified consisting of two suicides and six undetermined manners. The average postmortem caffeine concentration was 140.4 mg/L. This is the largest case series reported to date of lethal caffeine intoxication. Large doses of prescription medications and/or over the counter medications were abused. No overdoses were from consumption of caffeine-containing foods. Comprehensive postmortem toxicological testing should test for caffeine to capture these rare deaths.

Tapentadol (Nucynta) is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe acute pain. Its efficacy is believed to be due to μ-opioid receptor agonist activity and inhibition of norepinephrine reuptake resulting in increased norepinephrine concentrations. There is only one other case in the literature relating to the toxicity of this agent or report of a fatality. This case report documents a case in which tapentadol was identified as the cause of death. The tapentadol concentration found in the heart blood submitted in this case was more than 20 times the upper limit of the therapeutic range. Possible mechanisms of death include respiratory depression, central nervous system depression, and serotonin syndrome. Based on the scene investigation and autopsy findings in this case, the medical examiner determined that the cause of death was narcotic (Nucynta) intoxication and the manner of death was undetermined.

The need for addressing posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing public health concern. Current PTSD management addresses psychiatric parameters of this condition. However, PTSD is not simply a psychiatric disorder. Traumatic stress increases the risk for inflammation-related somatic diseases and early mortality. The metabolic syndrome reflects the increased health risk associated with combat stress and PTSD. Obesity, dyslipidemia, hypertension, diabetes mellitus, and cardiovascular disease are prevalent among PTSD patients. However, there has been little appreciation for the need to address these somatic PTSD comorbidities. Medical professionals treating this vulnerable population should screen patients for cardiometabolic risk factors and avail themselves of existing preventive diet, exercise, and pharmacologic modalities that will reduce such risk factors and improve overall long-term health outcomes and quality of life. There is the promise that cardiometabolic preventive therapy complementing psychiatric intervention may, in turn, help improve the posttraumatic stress system dysregulation and favorably impact psychiatric and neurologic function. © 2013 S. Karger AG, Basel.

Cathinone derivatives (bath salts) have emerged as the latest drugs of abuse. 3,4-methylenedioxypyrovalerone (MDPV) is the primary active ingredient in bath salts used in this country. This article presents the second reported cause of death by MDPV intoxication alone. In April 2011, a delusional man was emergently brought to a hospital, where he self-reported bath salt usage. He became agitated, developed ventricular tachycardia, hyperthermia, and died. Comprehensive alcohol and drug testing was performed. Using the alkaline drug screen, heart blood contained 0.7 mg/L MDPV and peripheral blood contained 1.0 mg/L MDPV. His bizarre behavior with life-threatening hyperthermia was consistent with an MDPV-induced excited delirium state. MDPV is not yet found by routine immunoassay toxicology screens. Testing for MDPV should be considered in cases with a history of polysubstance abuse with stimulant type drugs, report of acute onset of psychogenic symptoms, excited delirium syndrome, or presentation in a hyperthermic state.

Epilepsy is a common chronic neurological disorder characterized by seizures. Mortality is significantly increased in patients with epilepsy. Sudden unexpected death in epilepsy (SUDEP) is the most common seizure-related category of death. A retrospective study of forensic autopsy cases from 2007 to 2009 at the Office of the Chief Medical Examiner (OCME) yielded a total of 104 sudden unexpected deaths directly or indirectly caused by an epilepsy/seizure disorder in the State of Maryland. Of these deaths, 74 cases met a general accepted definition of SUDEP. The age of SUDEP individuals ranged from 14 to 63 with the majority of subjects in the ages between 21 and 50 years (58 cases, 78.4%). Males were slightly more likely than females to die of SUDEP (male:female=1.5:1 based on the rate). The onset age of epilepsy was documented in 47.3% of cases (35/74) based on investigation and medical records. Of the 35 cases, 12 subjects had early onset epilepsy (onset ages 1-15 years) and 20 subjects had duration of epilepsy for more than 10 years. The majority of deaths (61 of the 74 cases, 82.4%) were unwitnessed. Death scene investigation showed that 71 deaths (95.9%) occurred inside their residence with 50 subjects (70.4%) found either in bed or on the bedroom floor near the bed. Forty-three out of 74 cases (58.1%) showed neuropathological lesions. Per history, 50 subjects were reported as being on anti-epileptic drugs (AEDs). However, postmortem toxicological analysis revealed that only 26 subjects (35.1%) had detectable AEDs. Of the 74 cases, seizure disorder or epilepsy was listed as primary cause of death in 66 cases and the term of SUDEP as official cause of death in only 8 cases. This report focuses on the characteristics of death scene investigation and postmortem examination findings of SUDEP cases.

Diabetic ketoacidosis (DKA) results from severe insulin deficiency and can be diagnosed at autopsy despite no known history of the disease. Diabetic ketoacidosis may be the initial manifestation of type 1 diabetes or may result from increased insulin requirement in type 1 diabetic patients. The purpose of this study was to determine the percentage of DKA death investigated by the Office of Chief Medical Examiner that was not associated with a known history of diabetes.Cases investigated by the Office of Chief Medical Examiner during a 6-year period whose cause of death was DKA were identified using a centralized database. To determine the percentage with known history of diabetes, investigation reports were reviewed for any documentation of this history. The toxicology reports of all DKA deaths were reviewed together with histologic slides, if available, for possible microscopic changes. Concentrations of vitreous glucose, vitreous acetone, and blood acetone were used to diagnose DKA in these autopsied cases.Nearly a third of all death from DKA (32 of 92 during a 6-year period) occurred in individuals who had no known history of diabetes, emphasizing the importance of regular physicals that include a check of glucose concentration, and especially if any warning signs are present. In a case of sudden death, it is recommended that the volatile toxicology analysis at a medical examiner's office should include tests for acetone concentration, which when elevated, together with an elevated vitreous glucose, indicates DKA.

Drugs derived from amphetamine, methamphetamine and their methylenedioxy- analogues, although being sold as plant food or bath salts, are being used as legal alternatives to scheduled amphetamine stimulants. These products often contain methylone, mephedrone and methylenedioxypyrovalerone (MDPV)--three amphetamine derivatives shown to have strong pharmacological effects. Four postmortem cases were analyzed for methylone, mephedrone and MDPV, with drug levels quantitated in multiple biological matrices. All four cases had detectable levels of methylone, with heart blood concentrations of 0.740, 0.118, 0.060 and 1.12 mg/L. Analysis of several tissue samples shows that methylone does not sequester in a particular tissue type after death. The average liver-to-blood ratio was 2.68. Two cases also had MDPV present, but insufficient data were collected to formulate a hypothesis on postmortem sequestration or redistribution. Two different extraction methods, as well as analysis of derivatized and underivatized methylone, show that the drug is suitable for analysis in either method. The cases are believed to show one instance of chronic methylone use, with a urine concentration of 38 mg/L.

Compounds belonging to several scaffolds-quinazolines, quinolines and quinoxalines-were designed and synthesized as Raf kinase inhibitors. Scaffolds were assessed for in vitro Braf(V600E) inhibition, and overall kinase selectivity. Pharmacokinetic parameters for one of the scaffolds were also determined.

Nitric oxide (NO) has long been known as endothelium-derived relaxing factor. It is a vasodilator, modulating vascular tone, blood pressure and hemodynamics, a role exploited by nitrate donor therapy for angina, heart failure, pulmonary hypertension and erectile dysfunction. In addition, its powerful antioxidant, anti-inflammatory and antithrombotic actions are antiatherogenic with antiatherothrombotic impact. NO signaling modulates skeletal muscle and myocardial contractility and metabolism and is intimately linked with insulin signaling. Vascular and muscle NO signaling coordinate skeletal muscle and myocardial energy demand with supply and are critical for both carbohydrate and fatty acid total-body homeostasis. NO signaling in mitochondria underlies much of NO’s metabolic effect, which, at low physiologic levels, links cellular energy demand with mitochondrial energy supply, while beneficially affecting mitochondrial oxidative stress and calcium handling. Mitochondria are also the site for the life-threatening deleterious effects arising from inflammation-related excessive NO levels. NO-deficient states are characterized by cell senescence, oxidative stress, inflammation, endothelial dysfunction, vascular disease, insulin resistance and type 2 diabetes mellitus. NO-enriching therapy would be expected to be of benefit not only for its hemodynamic but also for its metabolic impact. In contrast, strategies are needed to curtail excessive NO in states such as septic shock.

Assigning a level of significance to cyanide concentrations found in the blood of fire victims is often hampered by the fact that cyanide is inherently unstable in cadavers and in stored blood samples. A few researchers have proposed that sodium fluoride can be used to minimize the instability of cyanide in blood samples; however, controlled studies have not been performed to support validation of this hypothesis. To test the sodium fluoride hypothesis, both treated and control blood samples from 14 autopsied fire victims were tested over a 25-30 day period. A 2% concentration of sodium fluoride was added to the blood samples at the start of testing and the samples were refrigerated between testing intervals. Cyanide concentrations in the treated and control samples were measured between 9 and 11 days post treatment and between 25 and 30 days post treatment. A statistically significant difference was not present between blood cyanide concentrations in treated and control samples between 9 and 11 days. During this time period, although there were small statistically significant increases in both treated and untreated samples the fluctuations were minor. Since the treated and control samples did not exhibit instability between 9 and 11 days, it is not surprising that the sodium fluoride appeared to have no effect. However, a statistically significant difference between blood cyanide concentrations in treated and control samples was observed between 25 and 30 days. Those samples treated with sodium fluoride showed a reduction in blood cyanide variability with virtually no overall change, over a 25-30 day period when compared to control samples, while unconditioned samples showed a significant, average increase of 35%. Based on the findings of this study, it is recommended that 2% sodium fluoride be added to blood samples obtained from fire victims to reduce cyanide instability due to bacteriological activity.

A death involving abuse of propylhexedrine and mitragynine is reported. Propylhexedrine is a potent α-adrenergic sympathomimetic amine found in nasal decongestant inhalers. The decedent was found dead in his living quarters with no signs of physical trauma. Analysis of his computer showed information on kratom, a plant that contains mitragynine, which produces opiumlike effects at high doses and stimulant effects at low doses, and a procedure to concentrate propylhexedrine from over-the-counter inhalers. Toxicology results revealed the presence of 1.7 mg/L propylhexedrine and 0.39 mg/L mitragynine in his blood. Both drugs, as well as acetaminophen, morphine, and promethazine, were detected in the urine. Quantitative results were achieved by gas chromatography-mass spectrometry monitoring selected ions for the propylhexedrine heptafluorobutyryl derivative. Liquid chromatography-tandem mass spectrometry in multiple reactions monitoring mode was used to obtain quantitative results for mitragynine. The cause of death was ruled propylhexedrine toxicity, and the manner of death was ruled accidental. Mitragynine may have contributed as well, but as there are no published data for drug concentrations, the medical examiner did not include mitragynine toxicity in the cause of death. This is the first known publication of a case report involving propylhexedrine and mitragynine.

Two cases are reported involving the abuse of extended-release oxymorphone hydrochloride tablets (Opana® ER) in combination with alprazolam (Xanax®). Two juvenile females were discovered unresponsive and hypoxic by a male acquaintance. The trio had reportedly crushed and snorted Opana ER tablets and consumed Xanax for recreational purposes. Emergency personnel were able to stabilize one female. The second female was pronounced dead at the scene. Blood and urine samples from the surviving female were collected at the trauma center between 48 and 96 h post incident. Toxicology results showed the presence of oxymorphone, doxylamine, dextromethorphan, alprazolam, α-hydroxyalprazolam, oxazepam, and temazepam in her urine. No drugs were detected in her blood. Toxicology on the deceased female revealed the presence of 0.13 mg/L oxymorphone and 0.04 mg/L alprazolam in her blood. Gastric contents contained 0.25 and 0.93 mg/L of oxymorphone and alprazolam, respectively. Oxymorphone, alprazolam, and α-hydroxyalprazolam were present in her urine. Quantitative results were achieved by gas chromatography-mass spectrometry monitoring selected ions for the oxime-oxymorphone-trimethylsilyl derivative, alprazolam, and the α-hydroxyalprazolam tert-butyldimethylsilyl derivative. The established linearity ranges for the opiate and benzodiazepine methods were 0.050-3.000 and 0.025-1.000 mg/L, respectively. The cause of death was reported as multiple drug toxicity, and the manner of death was accidental.

Levetiracetam, hydroxycarbazepine (the primary product of oxcarbazepine use), and topiramate were quantified using the acid/neutral drug screening procedure employed by this laboratory. Briefly, blood or tissue homogenate spiked with an internal standard (cyclopentobarbital) was buffered to pH 5 and applied to Chem Elut® columns. The columns were washed with methylene chloride, collected, and evaporated to dryness. The residue was reconstituted with 0.033 M trimethylanilinium hydroxide and injected into a gas chromatograph equipped with a DB-5 analytical column (25 m × 0.32-mm i.d.) and a nitrogen-phosphorus detector. A calibration curve using four calibrators ranging in concentration from 2 to 20 mg/L was used for quantification. Despite the limited number of cases for each drug, there were some trends suggested by the data. None of the drugs displayed significant differences in concentration between the heart blood and peripheral (subclavian) blood specimens. Only the hydroxycarbazepine quantifications in one case (case 5) showed significant differences between the two blood sites. This is consistent with other acid/neutral drugs such as acetaminophen and meprobamate. It also appears that the liver and kidney concentrations of the three drugs are on the same order of magnitude as the blood concentrations. Only the levetiracetam concentration in one case (case 3) reflected a liver or kidney concentration greater than 5 times the blood concentration.

A series of arylaminobenzimidazoles was designed and synthesized as Raf kinase inhibitors. Exploration of the structure-activity relationship resulted in compounds that are potent in vitro and show desirable in vivo properties.

Delta9-Tetrahydrocannabinol (THC) is the main psychoactive compound present in marijuana. THC can also be found, as a contaminant, in some commercially available hemp products marketed in health food stores and on the internet as a good source of essential fatty acids. The products range from oil to alcoholic beverages to nutritional bars to candies, with oil being the most popular and commonly available. The analytical results are separated into two groups, products tested prior to and after publication of 21 CFR Part 1308, "clarification of listing of tetrahydrocannabinols." The data presented are a summary of 79 different hemp products tested for THC. THC was separated by a liquid-liquid or solid-liquid extraction, depending upon the product matrix. THC concentrations range from none detected to 117.5 microg THC/g material. Typical limits of detection for the assay (depending on matrix) are 1.0-2.5 microg THC/g material. Products that were of aqueous base (beer, tea) had much lower limits of detection (2.5 ng/mL). No THC was detected in 58% of the products from group 1 and 86% of the products from group 2. The amounts indicate that THC levels in currently marketed hemp products are significantly lower than in those products available before 2003 and reported in previous studies. The results reported here may be used as a general guideline for the THC content of hemp products recently found in the marketplace today.

Two fatal overdoses of the calcium channel blocker amlodipine are described. Postmortem samples were screened for volatiles and therapeutic and abused drugs. Amlodipine was measured by liquid chromatography-atmospheric pressure photoionization-mass spectrometry. The heart blood amlodipine concentrations for the two cases were 2.4 and 0.95 mg/L, and amlodipine was quantified in all other tissues. In the first case, venlafaxine and norvenlafaxine were also found, and the angiotensin receptor antagonist olmesartan was tentatively identified. The concentrations of amlodipine are compared with previously reported fatal and nonfatal overdoses. The medical examiners ruled in both cases that the manner of death was suicide and the causes of death were mixed drug intoxication and amlodipine intoxication.

The case of a 57-year-old white female who was found deceased at home by her husband is presented. A suicide note was found at the scene. No remarkable findings were observed at autopsy. Comprehensive toxicological analysis of the heart blood identified ethanol (0.16 g/dL), diazepam (1.1 mg/L), and tizanidine (2.3 mg/L). Blood concentrations of tizanidine following therapeutic use do not exceed 0.025 mg/L. The medical examiner ruled that the cause of death was combined ethanol and multiple drug intoxication, and the manner of death was suicide.

This study was designed to supplement previous attempts to establish an accurate range of normal endogenous gamma-hydroxybutyrate (GHB) concentrations in random antemortem urine samples. Furthermore, its purpose was to ascertain the effect of gender, race, age, medications, and select medical conditions on endogenous concentrations of GHB in urine and the proposed endogenous urinary GHB cutoff of 10 microg/mL. Urine samples (n = 207) were provided by subjects who reported that they had never used GHB. As part of the collection process, subjects also completed a short survey to collect information about gender, race, age, orally ingested medications, and select medical conditions. All specimens were analyzed in duplicate for the presence of endogenous GHB using a previously reported headspace gas chromatography-mass spectrometry method. The data were analyzed for tendencies among different population groups. GHB concentrations ranged from 0.00 to 2.70 microg/mL in all specimens, with a median concentration of 0.24 microg/mL. Males (n = 130) had an average endogenous GHB concentration of 0.27 microg/mL (0.00-2.70 microg/mL), whereas females (n = 77) averaged 0.29 microg/mL (0.00-0.98 microg/mL). Select medical conditions and participants' race, age ranges, and medications that were used within 48 h prior to collection were also evaluated. We believe this to be the most comprehensive study on endogenous GHB concentrations in urine to date. The results of this study will aid the interpretation of low GHB concentrations measured in urine samples, particularly in investigations of drug-facilitated crimes.