Steven W. Fleming

Two cases of intoxication with new synthetic opioid, U-47700

Abstract Background: Novel substances often referred to as “designer drugs” have emerged as drugs of abuse, and recognition of these is difficult as routine blood and urine screening tests do not detect these agents. U-47700 is a synthetic selective μ-opioid agonist that can be bought online for as little as

Analysis of U-47700, a Novel Synthetic Opioid, in Human Urine by LC–MS–MS and LC–QToF

40 per gram. We report two patients presenting after insufflation of U-47700, with subsequent confirmation of this substance in urine samples. Case details: A 26-year-old man and 24-year-old woman insufflated a substance they believed to be “synthetic cocaine.” The man was found down with cyanosis and agonal respirations. He was intubated and taken to hospital where he recovered well with supportive care. The woman presented with anxiety, tremors and drowsiness and was admitted for observation. Urine samples from both patients were analyzed using GC/MS/MS and LC/QToF, and U-47700 was isolated in both cases. No other opioids were detected. Discussion: These cases are concerning because U-47700 is a relatively new agent that is easy to obtain over the internet and has the potential to cause significant morbidity and mortality.

Quantitation of Cocaine, Benzoylecgonine, Ecgonine Methyl Ester, and Cocaethylene in Urine and Blood Using Gas Chromatography-Mass Spectrometry (GC-MS)

The illicit drug market has rapidly evolved from synthetic cannabinoids to cathinone derivatives and now a new emerging threat of synthetic opioids. These compounds were mostly developed by pharmaceutical companies during drug discovery. The new psychoactive substances are not routinely covered in drug screening and may go undetected. Recently fentanyl analogous, AH-7921, MT-45 and now U-47700 have been encountered in clinical and forensic casework. U-47700 is gaining popularity on drug user forms as a legal alternative to heroin. It is a µ-receptor agonist that is part of the trans-1-2-diamine opioid analgesic drug class developed by The Upjohn Company in an attempt to develop a non-addicting analgesic. A LC-MS-MS method was developed and validated to detect and quantify U-47700. Additional analysis was conducted with an LC-QToF to identify the presence of the parent drug and metabolites. A total of four cases have been evaluated by the LC-MS-MS methodology which has an analytical range of 1-1,250 ng/mL and limit of detection of 1 ng/mL. The concentration of U-47700 in urine specimens ranged from below the limit of quantification to 224 ng/mL. The ToF analysis detected the presence of suspected phase I demethylated metabolites that may assist future analysis of this compound. The prevalence of designer opioids in casework highlights the importance of analysis for new psychoactive substances. Traditional opiates/opioids were not detected in the presented cases, but the available case histories revealed an opioid toxidrome. These findings suggest that U-47700 drug may cause significant morbidity and mortality within the United States as an emerging drug threat.

Addressing Hazards from Unscheduled Novel Psychoactive Substances as Research Chemicals: The Case of U-50488

Cocaine, a stimulant, is a commonly abused drug. Cocaine and its metabolites are measured in various biological specimens for clinical and forensic purposes. Urine or plasma or serum is spiked with deuterated internal standards cocaine-d3, benzoylecgonine-d3, ecgonine methyl ester-d3, and cocaethylene-d3 and buffered with phosphate buffer. The drugs in the sample are extracted by cation-exchange solid phase extraction. The drugs from the solid phase cartridge are eluted and the eluent is dried under the stream of nitrogen. The residue is incubated with pentafluoropropionic acid anhydride and pentafluoropropanol to form pentafluoropropionyl derivatives of ecgonine methyl ester and benzoylecgonine. Cocaine and cocaethylene are refractory to derivatization. The extract is dried, reconstituted in ethyl acetate, and injected into gas chromatography mass-spectrometry analyzer. Quantitation of the drugs in the samples is made, using selected ion monitoring, from a 3-point calibration curve.

To Dab or Not to Dab: Rising Concerns Regarding the Toxicity of Cannabis Concentrates

Increased experimentation with easily accessible synthetic opioids is posing a hazard to the public. We discuss one such synthetic opioid, U-50488. Much is unknown about U-50488; however, due to its structural similarity to U-47700, there is possible risk associated with its use. Curtailing the use of synthetic opioids such as U-50488 will require a concerted effort targeting multiple problems.

A little “dab” will do ya’ in: a case report of neuro-and cardiotoxicity following use of cannabis concentrates

Cannabis use is steadily rising in the United States. As the popularity of marijuana rises, new varieties of cannabis-related products are becoming available. Dabs are cannabis concentrates gaining notoriety for their significant amounts of tetrahydrocannabinol (THC) that are ultimately vaporized and inhaled for their effect. Herein, we provide an overview of recent cases of dabbing to bring awareness to the clinicians, of the significant adverse effects associated with dabs including psychosis, neurotoxicity, and cardiotoxicity.

AH-7921: A review of previously published reports

Abstract Context: The use of marijuana and cannabis concentrates is increasing, especially following decriminalization in several states. Psychosis and cardiotoxicity have been reported following cannabis use; however, myocardial injury from “dabbing” has not yet been reported. We report a case of hyperthermia, tachycardia, hypertension, severe agitation, neuro-, and cardiotoxicity following the use of “dabs” where there is concomitant confirmatory biological and sample testing. Case details: A 17-year-old athletic man developed agitation requiring sedation and intubation for safety, with peak systolic blood pressures in the 190s and hyperthermia (to 102 °F). He developed elevated serum troponins with persistent tachycardia despite sedation and no clear non-intoxicant etiology. It was discovered that the patient had recently been “dabbing”; an exhaustive search of his home found a sample of the “dabs” which was analyzed along with a comprehensive urine drug screen by tandem liquid mass spectroscopy (t-LCMS) for confirmation. Discussion: Tetrahydrocannabinol (THC) has been increasingly associated with agitation and cardiotoxicity, while cannabidiol (CBD) has been associated with neuroprotective, inhibitory states. We propose that increasing concentrations of THC as well as THC:CBD ratios seen in cannabis concentrates such as “dabs” may cause agitation and end-organ damage through sympathomimetic and serotonergic pathways.

U-47700: An Emerging Threat

ABSTRACT AH-7921 is a synthetic opioid that was developed in the early 1970s. It has resulted in several fatal and nonfatal intoxications, despite not having approval from the US Food and Drug Administration. To date, AH-7921 is listed as a schedule I drug, and there have been no clinical trials exploring the safety of AH-7921. Herein, we provide an analysis of existing case reports available in the literature regarding AH-7921. We searched PubMed, Scopus, Web of Science, and EBSCO for articles (up until December 2017) using the terms “AH-7921” and “AH7921.” In total, 48 articles were identified, and 5 articles were included in our review. A total of 14 cases were found, of which 13 resulted in fatalities. The oral route of administration was reported in two cases, and most cases reported use of concomitant pharmaceutical agents. Pulmonary edema was the most common finding postmortem among deceased cases, with nine of the cases having heavier lungs. Overall, fatalities occurred with low and high concentrations of AH-7921 in the femoral blood. We strongly encourage toxicology screenings for this novel opioid to be included when an overdose of an opioid of unknown nature is suggested.

Shortcomings of Urine-Preferred Drug Screening on Post-Mortem Specimens

Illicit opioid use continues to be an ever-growing problem in the United States. The rise of synthetic opioids is an emerging threat that is beginning to draw attention over the past few years. Herein, we present an overview of the rise of a synthetic opioid known as U-47700. We describe U-47700s history, legal status, ease of obtainment, consequences of its use, and a proposal to increase the awareness of this synthetic opioid.

U-47700: A Clinical Review of the Literature

Abstract In counties with limited budgets, in order to save money on toxicology work, the request often comes from local medical examiners that screening for drugs on decedents be performed initially on urine and, if positive, to send blood for confirmation; negative urine results are not further evaluated. A study of known urine and blood drug screens was performed to evaluate the clinical and cost-effectiveness of this practice. Results of 401 autopsies were reviewed. In all, 11 decedents had both urine and blood drug screens performed. There were seven men and four women, mean age for both 39 years. In the urine drug screens, there were nine true positive tests, 17 false positives, 45 true negatives, and five false negatives; sensitivity 64%, specificity 73%. The savings in cost were theoretically 34%, but screening urine for drugs on post-mortem specimens does not appear to be an effective way to determine what drugs were present at the time of death. It is inexpensive, however. Still, in a screening practice for which so many of the results are not reliable, one must decide whether the money saved is worth the misleading results. Considering how many critical decisions about cause and manner of death are based on toxicology, it would seem unreliable to choose a urine-preferred practice.