Retrospective determination of regenerated nerve agent sarin in human blood by liquid chromatography–mass spectrometry and in vivo implementation in rabbit
| Autor: | Meir Avraham, Shlomit Dachir, Hani Dekel Jaoui, Shlomi Lazar, Avi Weissberg, Shlomi Baranes, Inbal Egoz, Shai Dagan, Moran Madmon, Avital Shifrovitch, Merav Blanca, Maor Elgarisi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Sarin Health Toxicology and Mutagenesis 010501 environmental sciences Toxicology Mass spectrometry Sensitivity and Specificity 01 natural sciences Fluorides 03 medical and health sciences chemistry.chemical_compound Limit of Detection Tandem Mass Spectrometry In vivo Liquid chromatography–mass spectrometry medicine Animals Humans Derivatization 0105 earth and related environmental sciences Nerve agent Detection limit Chromatography Human blood General Medicine 030104 developmental biology chemistry Solvents Female Rabbits Nerve Agents Chromatography Liquid Half-Life medicine.drug |
| Zdroj: | Archives of Toxicology. 94:103-111 |
| ISSN: | 1432-0738 0340-5761 |
| Popis: | The highly toxic nerve agent sarin (o-isopropyl methyl-phosphonofluoridate, GB) has been used in several armed conflicts and terror attacks in recent decades. Due to its inherent high sensitivity, liquid chromatography–mass spectrometry (LC–MS/MS) has the potential to detect ultratrace levels of fluoride-regenerated G and V agents after appropriate chemical derivatization. A new method for the retrospective determination of exposure to sarin was developed. The method is based on sarin regeneration from blood using the fluoride-induced technique followed by derivatization with 2-[(dimethylamino)methyl]phenol (2-DMAMP) and LC–ESI–MS/MS (MRM) analysis. The validated method presents good linear response in the concentration range of 5–1000 pg/mL with a limit of quantitation (LOQ) of 5 pg/mL, 13.8% accuracy, 16.7% precision and a total recovery of 62% ± 9%. This new analytical approach has several advantages over existing GC/GC–MS-based methods in terms of sensitivity, specificity and simplicity, in addition to a short LC–MS cycle time of 12 min. The method was successfully applied in an in vivo experiment for retrospective determination of sarin in a rabbit exposed to 0.1 LD50 sarin (1.5 µg/kg, i.v.). GB-2-DMAMP was easily determined in samples drawn up to 11 days after exposure. The high S/N ratio (500) observed for the GB-2-DMAMP signal in the 11day sample poses the potential for an extended time frame of months for analysis with this new method for the retrospective detection of sarin exposure. To the best of our knowledge, this is the first report on LC–MS/MS trace analysis of regenerated GB from biological matrices. |
| Databáze: | OpenAIRE |
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