In this paper we report on the identification and full chemical characterization of isotonitazene (N,N-diethyl-2-[5-nitro-2-({4-[(propan-2-yl)oxy]phenyl}methyl)-1H-benzimidazol-1-yl]ethan-1-amine), a potent NPS opioid and the first member of the benzimidazole class of compounds being available in online markets. Interestingly, this compound was sold under the name etonitazene, a structural analogue. Identification of isotonitazene was performed by gas chromatography mass spectrometry (GC-MS) and liquid chromatography time-of-flight mass spectrometry (LC-QTOF-MS), the latter identifying an exact-mass m/z value of 411.2398. All chromatographic data indicated the presence of a single, highly pure compound. Confirmation of the specific benzimidazole regio-isomer was performed using 1 H and 13 C NMR spectroscopy, after which the chemical characterization was finalized by recording Fourier-transform (FT-IR) spectra. A live cell-based reporter assay to assess the in vitro biological activity at the μ-opioid receptor (MOR) revealed that isotonitazene has a high potency (EC50 of 11.1 nM) and efficacy (Emax 180% of that of hydromorphone), thus confirming that this substance is a strong opioid. Isotonitazene has not been previously detected, neither in powder form, nor in biological fluids. The high potency and efficacy of isotonitazene, combined with the fact that this compound was being sold undiluted, represents an imminent danger to anyone aiming to use this powder.

The opioid epidemic in the United States resulted in 42,000 deaths in 2016, 40% of which involved a prescription opioid. It is estimated that 2 million patients become opioid-dependent after elective, ambulatory surgery each year. There has been increased interest in quantifying the need for postoperative narcotic pain medications for a variety of surgical procedures. However, studies have been limited. We sought to quantify the analgesic usage after one of the most common operations performed in plastic surgery, bilateral breast reduction.In this prospective, observational study, sequential breast reduction patients were contacted by telephone on the evening of postoperative days 3 and 7. Patients were queried as to which analgesic medications were used on the day of the phone call. Data relating to dosage, frequency, and satisfaction with pain control were sought. Patients taking chronic narcotics, postoperative complications requiring surgical intervention, and those unable to be reached after multiple attempts were excluded.Complete data were obtained for 40 patients. Narcotic prescriptions were written for oxycodone, hydromorphone and tramadol, with the number prescribed ranging from 0 to 20 tablets. The median total number used was 6 tablets. Eighty percent of patients used a total of 10 tablets or less. Fifty percent of patients were using only nonnarcotic analgesia by postoperative day 3. Patient-reported satisfaction with pain control was overwhelmingly positive, with 95% being either somewhat satisfied or very satisfied with postoperative pain control. Of those taking any medication on postoperative day 3, only half were using a nonsteroidal anti-inflammatory drug (NSAID) as part of their pain regimen.The number of tablets prescribed after breast reduction surgery varies considerably, and there is no consensus regarding the appropriate number to prescribe. Currently, few patients use all the medication prescribed to them, indicating a high rate of overprescribing. The overwhelming majority are satisfied with their pain control. Most patients use less than 10 tablets of narcotic pain medication after surgery. Acetaminophen is widely used as an adjunct but NSAIDs remain underutilized. Based on these data, we recommend that breast reduction patient's pain is best managed with acetaminophen, NSAIDs, and expectation management.

Hydromorphone and oxymorphone are semisynthetic derivatives of morphine and potent opiate agonists which are used predominantly to treat moderate-to-severe pain. Neither hydromorphone nor oxymorphone have been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.