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.
Oxidative damage is a naturally occurring process where reactive oxygen species (ROS) attack and disrupt normal cellular function, however, these effects become elevated during a stress event, such as ischemia/reperfusion or seizure. One result of oxidative stress is lipid peroxidation, where ROS attack free unsaturated fatty acids forming lipid hydorperoxides, which then breakdown to form secondary products acrolein, 4-hydroxynonenal, and malondialdehyde (MDA) resulting in irreversible membrane damage and ultimately cell death. Described here is a CE – fluorescence method for the determination of MDA in conjunction with in vivo microdialysis sampling. MDA was derivatized with thiobarbituric acid under acidic conditions for 20 minutes and injected directly onto the capillary without any pretreatment. This method provided a limit of detection of 25 nM (S/N = 3) and a linear range of 25-2400 nM (1.8-174 ng/ml). This method was used to quantify MDA in rat heart, muscle, liver, and brain dialysate.
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