At present, therapeutic drug monitoring is the standard in pharmacotherapy using medications with a narrow therapeutic index or showing serious adverse effects, such as in the case of ibrutinib. A technique commonly used for this purpose is liquid chromatography-tandem mass spectrometry combined with isotope dilution in sample processing. Although this method provides a high degree of reliability, its use can be complicated with some specific factors and does not guarantee trouble-free analysis. This paper is focused on investigating issues related to the differential adsorption of ibrutinib and its D4, D5 and 13C6 isotopically labeled analogues combined with instrument-specific carry-over. The results of the research point out the significantly different adsorption behavior of ibrutinib in fluidics of LC-MS compared with that of its D4, D5 and 13C6 stable isotope labeled analogues, showing preferential adsorption of non-labeled compound. The investigation also pointed to a strong affinity of ibrutinib to polymeric surfaces under specific conditions, which has to be taken into consideration during sample preparation and analysis. Our work opens a new field for the discussion of scarcely reported problem related to the use of stable isotope labeled internal standards in LC-MS/MS analysis.

Department of Clinical Biochemistry and Diagnostics University Hospital and Faculty of Medicine Hradec Králové Sokolská 581 500 05 Hradec Králové Czech Republic

Department of Medical Biochemistry Faculty of Medicine in Hradec Kralove Charles University Zborovská 2089 500 03 Hradec Králové Czech Republic

Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Faculty of Pharmacy Charles University Akademika Heyrovského 1203 500 05 Hradec Králové Czech Republic

Institute of Organic Chemistry and Biochemistry The Czech Academy of Sciences Flemingovo nám 2 166 10 Prague 6 Czech Republic

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