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J Pharm Biomed Anal ; 247: 116253, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-38810334

RÉSUMÉ

Consumption of misidentified foraged mushrooms containing bicyclic amanitin octapeptides is a worldwide public health and veterinary problem, being considered one of the deadliest accidental human and canine food ingestion due to acute liver failure (ALF). Reversal of advanced ALF and complete clinical recovery can be achieved following definitive removal of accumulated amatoxin laden bile from the gallbladder. An accurate means of quantifying amanitin content in aspirated bile is, therefore, urgently needed. Building on our prior work validating a method to detect and quantify amanitin in hepatic autopsy tissue, the development of an accurate method of measuring α- and ß-amanitin in aspirated gallbladder bile was performed to evaluate the efficiency of this emergency procedure applied as a clinical treatment for intoxicated patients. A solid-phase extraction (SPE) procedure was optimized followed by detection based on ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Low resolution mass spectrometry (LRMS) was compared with high resolution (HRMS) by the validation of UHPLC-MS/MS (triple quadrupole MS) and UHPLC-ToF-MS (time-of-flight MS). Both methods were able to detect amatoxins in bile with limits of detection and quantification ranging from 2.71 to 3.46 µg.kg-1, and 8.36-9.03 µg.kg-1 for α-amanitin and, 0.32-1.69 µg.kg-1 and 0.55-5.62 µg.kg-1 for ß-amanitin, respectively. Validation was completed with the evaluation of linearity, specificity, robustness, recovery, and precision following the ICH guidelines and CIR 808/2021. The validated methods were finally applied to bile samples obtained 48-96 hours + post-ingestion from 4 amatoxin poisoning patients who underwent gallbladder drainage procedures in Vietnam, Canada, and California. Gallbladder bile from patients with amatoxin mushroom poisoning contained significant amanitin content, even when aspirated several days post-ingestion, thus confirming the important role of enterohepatic circulation in amatoxin hepatotoxicity. This work represents a high and unique analytical throughput in amanitin poisoning allowing to efficiently respond to this fatal health problem.


Sujet(s)
Amanitines , Bile , Limite de détection , Spectrométrie de masse en tandem , Bile/composition chimique , Chromatographie en phase liquide à haute performance/méthodes , Amanitines/analyse , Amanitines/composition chimique , Humains , Spectrométrie de masse en tandem/méthodes , Extraction en phase solide/méthodes , Reproductibilité des résultats , alpha-Amanitine/analyse , alpha-Amanitine/composition chimique , Intoxication par les champignons/diagnostic
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