STANOVENÍ AMIODARONU A DESETHYLAMIODARONU V SRDEČNÍM HROTU PRASATE DOMÁCÍHO POMOCÍ KAPALINOVÉ CHROMATOGRAFIE S HMOTNOSTNÍ SPEKTROMETRIÍ

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Title in English Liquid chromatography mass spectrometry of amiodarone and desethylamiodarone in heart apex of pigs
Authors

GREGOROVÁ Jana NOVOTNÁ Lucie ŠMAK Pavel ODEHNALOVÁ Eva STÁREK Zdeněk CALUORI Guido PEŠ Ondřej

Year of publication 2020
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Amiodarone (AMD) has been used successfully in human medicine as an antiarrhythmic since the 1970s according to the Vaughan-Williams classification for the treatment of ventricular tachycardias and atrial fibrillation. The mechanism of action of AMD is mainly in the blockade of K+ channels, which leads to a prolongation of the QT interval and a prolongation of the refractory period. Side effects include bradycardia, hypotension and Torsades de pointes - a specific type of abnormal heart rhythm leading to sudden heart death. The biotransformation of AMD consists mainly of the conversion of the cytochrome CYP3A4 to the therapeutically active desethylamiodarone (DEA). Both AMD and DEA are lipophilic in nature and 96% bound to plasma proteins; therefore, they are primarily excreted from the body by bile. Adverse reactions are associated with inhibition of some CYP450 enzymes, but also with accumulation in the tissues from which they are gradually released. Thus, the plasma concentration does not correspond to the overall bioavailability of AMD and DEA in the body. The aim of our work was to introduce a simple LC-MS method for the determination of AMD and DEA in soft tissues, and compare their concentrations with plasma levels. Analyzes were obtained from cardiac tissue by liquid-liquid extraction into hexane. Labeled D4-amiodarone and D4-desethylamiodarone were used as internal standards. The results obtained answer the question of how effectively AMD and DEA accumulate in the heart tip after administration of AMD at a concentration of 5; 10 and 15 mg / kg after i.v. administration as an hourly infusion.
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