Search

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]