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Rationale: Tramadol (T) is a strong painkiller drug that belongs to the opioid analgesic group. Several accidental intoxication cases after oral administration of T have been reported in the past decade. Tramadol, its derivatives, and metabolites present information‐limited mass spectra with one prominent peak representing the amine‐containing residue; therefore, their structural determination based on both electron impact mass spectrometry (EI‐MS) and ESI‐MS/MS spectra could be misleading. Methods: A novel analytical method for the structural elucidation of tramadol, its four homologs, and its two main phase I metabolites (N‐desmethyltramadol and O‐desmethyltramadol) was developed using chemical modification and liquid chromatography–high‐resolution tandem mass spectrometry (LC‐HR‐MS/MS) with Orbitrap technology. Results: After chemical derivatization, each of the investigated T series exhibited informative mass spectra that enabled better exposition of their structures. The developed method was successfully implemented to explicitly identify the structures of tramadol and its N‐desmethyltramadol metabolite in urine samples at low ng/mL levels. Conclusions: An efficient derivatization‐aided strategy was developed for rapidly elucidating the structure of tramadol‐like compounds. The method is intended to assist forensic chemists in better diagnosing T and its analogs and metabolites in clinical or forensic toxicology laboratories. [ABSTRACT FROM AUTHOR]

Rationale: Sodium azide (NaN3) is a toxic chemical agent to humans by ingestion and inhalation with a growing number of intentional exposures and accidental cases over the last few decades. Due to its low molecular weight and lack of any chromophore, its retention and detection by reverse‐phase liquid chromatography–ultraviolet–mass spectrometry methods are a challenging task. Methods: To be able to confirm azide exposure, we have developed a method to identify azide in both beverages and bodily fluids. The identification of azide (N3−) is based on derivatization with N‐(2‐(bromomethyl)benzyl)‐N,N‐diethylethanaminium bromide (CAX‐B) at 25°C for 15 min followed by LC/ESI‐MS/MS analysis, with no other sample preparation. Results: The azide after derivatization (CAX‐N3) was stable, retainable by LC and sensitively detected by selected reaction monitoring. The ESI‐MS/MS fragmentation of the M+ precursor ion produced characteristic product ions at m/z 118, 100, 91 and 86. The calibration curves for CAX‐N3 showed linearity over two orders of magnitude with R2 value of 0.99. Low limits of identification of 0.1–0.5 ng/mL were obtained in all investigated matrices (drinking water, tea, orange juice, plasma and urine). Conclusions: Compared with previously reported chromatography‐based methods, this method that was based on derivatization and LC/ESI‐MS/MS analysis was substantially more sensitive, simpler and faster. The method can be used for forensic investigation to confirm azide exposure from fatal use to much smaller intoxication dose. [ABSTRACT FROM AUTHOR]

A novel COVID-19 vaccine (BriLife®) has been developed by the Israel Institute for Biological Research (IIBR) to prevent the spread of the SARS-CoV-2 virus throughout the population in Israel. One of the components in the vaccine formulation is tris(hydroxymethyl)aminomethane (tromethamine, TRIS), a buffering agent. TRIS is a commonly used excipient in various approved parenteral medicinal products, including the mRNA COVID-19 vaccines produced by Pfizer/BioNtech and Moderna. TRIS is a hydrophilic basic compound that does not contain any chromophores/fluorophores and hence cannot be retained and detected by reverse-phase liquid chromatography (RPLC)-ultraviolet (UV)/fluorescence methods. Among the few extant methods for TRIS determination, all exhibit a lack of selectivity and/or sensitivity and require laborious sample treatment. In this study, LC–mass spectrometry (MS) with its inherent selectivity and sensitivity in the multiple reaction monitoring (MRM) mode was utilized, for the first time, as an alternative method for TRIS quantitation. Extensive validation of the developed method demonstrated suitable specificity, linearity, precision, accuracy and robustness over the investigated concentration range (1.2–4.8 mg/mL). Specifically, the R2 of the standard curve was >0.999, the recovery was >92%, and the coefficient of variance (%CV) was <12% and <6% for repeatability and intermediate precision, respectively. Moreover, the method was validated in accordance with strict Good Manufacturing Practice (GMP) guidelines. The developed method provides valuable tools that pharmaceutical companies can use for TRIS quantitation in vaccines and other pharmaceutical products. [ABSTRACT FROM AUTHOR]

Rationale: The identification of V‐type nerve agents poses an analytical challenge. Their spectra obtained by electron ionization mass spectrometry (EI‐MS) and electrospray ionization tandem mass spectrometry (ESI‐MS/MS) are dominated by ions originating from the N,N‐dialkylaminoethyl moiety, while ions representative of the alkyl phosphonothiolate part are absent from the spectra or present at negligible abundance. Hence, analogs or isomers with the same amine residue exhibit similar mass spectral patterns, leading to unavoidable ambiguity in their identification. Methods: Chemical derivatization was utilized for the structural elucidation of a series of five V‐type nerve agents, including O‐ethyl S‐(2‐diisopropylamino)ethyl methylalkyl phosphonothiolate (VX), O‐isobutyl S‐(2‐diethylamino)ethyl methylalkyl phosphonothiolate (RVX) and O‐ethyl S‐(2‐diethylamino)ethyl methylalkyl phosphonothiolate (VM). The procedure consisted of "in‐vial" oxidation of the tertiary amine group with 3‐chloroperbenzoic acid (m‐CPBA) at ambient temperature followed by liquid chromatography (LC)/Orbitrap‐ESI‐MS/MS analysis with no other sample preparation. Results: The generated N‐oxide of the V‐type nerve agents altered the charge distribution occurring during fragmentation and produced informative ESI‐MS/MS spectra characteristic of the alkyl phosphonothiolate structure, enabling a higher degree of certainty in their identification. Moreover, two VX isomers possessing an identical tertiary amine moiety that coeluted at practically the same retention time and displayed high mass spectral similarity were easily differentiated, and their structures elucidated once derivatized. Conclusions: In contrast to the ESI‐MS/MS spectra of the V‐type nerve agents, which exhibited mostly/only information on the amine‐containing residue, the ESI‐MS/MS spectra of the V‐type nerve agent N‐oxides revealed ions indicative of both the alkyl phosphonothiolate and the amine parts, enabling their reliable structural elucidation. [ABSTRACT FROM AUTHOR]

Metallo-supramolecular polymers offer a highly controllable platform for sensing. Their modular characteristics obtained by the ability of varying both building blocks, the metal ion and the organic ligand, provide tunability of their optical and chemical properties. Specifically, polymers based on lanthanide ions and conjugated aromatic ligands exhibit enhanced luminescence properties that can be altered by external stimulation. Herein, using europium-based polymers, we demonstrate the ability to detect different pharmaceutical amines, including in complex biological media, based on their luminescence quenching efficiency as a result of their polymer dissociation capacity. A combination of absorption, luminescence, and NMR measurements reveals combined static and dynamic quenching mechanisms that enable selective sensing of strong basic amines with high p K a values.