Development of solvent-free ambient mass spectrometry for green chemistry applications.

Green chemistry minimizes chemical process hazards in many ways, including eliminating traditional solvents or using alternative recyclable solvents such as ionic liquids. This concept is now adopted in this study for monitoring solvent-free reactions and analysis of ionic liquids, solids, and catalysts by mass spectrometry (MS), without using any solvent. In our approach, probe electrospray ionization (PESI), an ambient ionization method, was employed for this purpose. Neat viscous room-temperature ionic liquids (RTILs) in trace amounts (e.g., 25 nL) could be directly analyzed without sample carryover effect, thereby enabling high-throughput analysis. With the probe being heated, it can also ionize ionic solid compounds such as organometallic complexes as well as a variety of neat neutral solid chemicals (e.g., amines). More importantly, moisture-sensitive samples (e.g., [bmim][AlCl4]) can be successfully ionized. Furthermore, detection of organometallic catalysts (including air-sensitive [Rh-MeDuPHOS][OTf]) in ionic liquids, a traditionally challenging task due to strong ion suppression effect from ionic liquids, can be enabled using PESI. In addition, PESI can be an ideal approach for monitoring solvent-free reactions. Using PESI-MS, we successfully examined the alkylation of amines by alcohols, the conversion of pyrylium into pyridinium, and the condensation of aldehydes with indoles as well as air- and moisture-sensitive reactions such as the oxidation of ferrocene and the condensation of pyrazoles with borohydride. Interestingly, besides the expected reaction products, the reaction intermediates such as the monopyrazolylborate ion were also observed, providing insightful information for reaction mechanisms. We believe that the presented solvent-free PESI-MS method would impact the green chemistry field.

Acute Intoxications Involving Valerylfentanyl Identified at the New York City Office of Chief Medical Examiner.

The detection of novel fentanyl analogs in both seized drugs and toxicological specimens has presented a significant challenge to laboratories with respect to identification, sourcing reference drug standards, the time required for method development and ensuring sufficient method sensitivity. The New York City Office of Chief Medical Examiner has included testing for valerylfentanyl as part of a panel of synthetic opioids since May 2017 but did not identify the first valerylfentanyl-positive case until July 2018. Unlike many other illicit fentanyl analogs that were briefly identified before being replaced with a new analog, valerylfentanyl has persisted over time and continues to be identified in New York City acute polydrug intoxications. Since July 2018, a total of 69 cases were identified to be valerylfentanyl positive, but there were no cases where it was the sole intoxicant. Eighty-four percentage of decedents were male, with the majority being Hispanic males (49%) between the ages of 50 and 59 years (39%). The cause of death in all 69 cases involved acute polydrug intoxications, while the manner of death was deemed an accident in 68 cases and undetermined in one case. Concentrations of valerylfentanyl in postmortem blood ranged from <0.10 to 21 ng/mL, with 44.9% (N = 31) of the concentrations at or below the lower limit of quantification (0.10 ng/mL) but above the limit of detection (0.05 ng/mL). Fentanyl was present in 100% of the cases and in higher concentrations (1.6-116 ng/mL). The most common other drug classes detected with valerylfentanyl were other opiates (76.8%), cocaine/metabolites (50.7%), benzodiazepines (29%) and ethanol (21.7%). Valerylfentanyl is a relatively unknown fentanyl analog with limited information in the scientific literature. This study presents the first publication detailing a series of postmortem cases involving valerylfentanyl in acute intoxications and includes key demographic information and femoral blood concentrations for improved interpretation and analysis.