Mechanism of atmospheric pressure chemical ionization of morphine, codeine, and thebaine in corona discharge-ion mobility spectrometry: Protonation, ammonium attachment, and carbocation formation
JOURNAL OF MASS SPECTROMETRY
Authors: Valadbeigi, Younes; Ilbeigi, Vahideh; Mirsharifi, Maryam S.
Abstract
Atmospheric pressure chemical ionizations (APCIs) of morphine, codeine, and thebaine were studied in a corona discharge ion source using ion mobility spectrometry (IMS) at temperature range of 100 degrees C-200 degrees C. Density functional theory (DFT) at the B3LYP/6-311++G(d,p) and M062X/6-311++G(d,p) levels of theory were used to interpret the experimental data. It was found that in the presence of H(3)O(+)as reactant ion (RI), ionization of morphine and codeine proceeds via both the protonation and carbocation formation, whereas thebaine participates only in protonation. Carbocation formation (fragmentation) was diminished with decrease in the temperature. At lower temperatures, proton-bound dimers of the compounds were also formed. Ammonia was used as a dopant to produce NH(4)(+)as an alternative RI. In the presence of NH4+, proton transfer from ammonium ion to morphine, codeine, and thebaine was the dominant mechanism of ionization. However, small amount of ammonium attachment was also observed. The theoretical calculations showed that nitrogen atom of the molecules is the most favorable proton acceptor site while the oxygen atoms participate in ammonium attachment. Furthermore, formation of the carbocations is because of the water elimination from the protonated forms of morphine and codeine.
Predictors of Prolonged Opioid Use After Initial Prescription for Acute Musculoskeletal Injuries in Adults A Systematic Review and Meta-analysis of Observational Studies
ANNALS OF INTERNAL MEDICINE
Authors: Riva, John J.; Noor, Salmi T.; Wang, Li; Ashoorion, Vahid; Foroutan, Farid; Sadeghirad, Behnam; Couban, Rachel; Busse, Jason W.
Abstract
Background: Opioids are frequently prescribed for acute musculoskeletal injuries and may result in long-term use and consequent harms. Purpose: To explore factors associated with persistent opioid use after its prescription for acute musculoskeletal injury. Data Sources: Searches of multiple electronic databases, without language restrictions, from inception to 6 January 2020, and reference lists of selected articles. Study Selection: Observational studies of adults with opioid prescriptions for outpatient acute musculoskeletal injuries, in an adjusted model, that explored risk factors for prolonged use. Data Extraction: 6 reviewers, working in pairs, independently extracted data, rated the quality of studies, and evaluated the certainty of evidence. Data Synthesis: 14 cohorts with 13 263 393 participants were included. The overall prevalence of prolonged opioid use after musculoskeletal injury for high-risk populations (that is, patients receiving workers' compensation benefits, Veterans Affairs claimants, or patients with high rates of concurrent substance use disorder) was 27% (95% CI, 18% to 37%). The prevalence among low-risk populations was 6% (CI, 4% to 8%; P for interaction < 0.001). Moderate-certainty evidence showed increased odds of persistent opioid use with older age (absolute risk increase [ARI] for every 10-year increase, 1.1% [CI, 0.7% to 1.5%]) and physical comorbidity (ARI, 0.9% [CI, 0.1% to 1.7%]). Low-certainty evidence suggested increased risk for persistent opioid use with past or current substance use disorder (ARI, 10.5% [CI, 4.2% to 19.8%]), prescriptions lasting more than 7 days (median ARI, 4.5%), and higher morphine milligram equivalents per day. Limitation: Sparse, heterogeneous data with suboptimal adjustment for potential confounders. Conclusion: Avoiding prescribing opioids for acute musculoskeletal injuries to patients with past or current substance use disorder, and restricting duration to 7 days or less and using lower doses when they are prescribed, are potentially important targets to reduce rates of persistent opioid use.