Abstract
Levosimendan is used in severe chronic cardiac insufficiency, also within the peri-operative setting. Real-life pharmacokinetic data in surgical patients is lacking, making therapeutic drug monitoring (TDM) of levosimendan, its pharmacologically active metabolite OR-1896, and its intermediate OR-1855 important. A simultaneous highly sensitive quantification of levosimendan and its metabolites in small-volume samples has not yet been described. Here, levosimendan (LLOQ 0.450 nM), OR-1896, and OR-1855 (LLOQ both 1.0 nM) were successfully quantified by LC-ESI-MS/MS after liquid-liquid extraction in 300 mu L of blood. A short C8 column under reversed-phase conditions enabled simultaneous and fast quantification of levosimendan in the negative and the metabolites in the positive ionization mode in a single run within 2 min. Interestingly and unexpectedly, constitutional isomers of levosimendan metabolites with identical mass transitions and similar retention times were observed in surgical patients' samples, which we identified as the metamizole metabolites 4-aminoantipyrine and 4-acetamidoantipyrine. A longer C8 column and a modified mobile phase enabled selective quantification of all analytes in a single run within 7 min. We developed, validated, and applied highly sensitive LC-ESI-MS/MS methods for simultaneous quantification of levosimendan and its metabolites, enabling efficient TDM of cardiac surgery patients even with additional metamizole administration.
Dokumententyp: | Zeitschriftenartikel |
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Fakultät: | Medizin |
Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
URN: | urn:nbn:de:bvb:19-epub-106707-1 |
Sprache: | Englisch |
Dokumenten ID: | 106707 |
Datum der Veröffentlichung auf Open Access LMU: | 11. Sep. 2023, 13:42 |
Letzte Änderungen: | 28. Sep. 2023, 21:08 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892 |