Differential adsorption of an analyte and its D4, D5 and 13C6 labeled analogues combined with instrument-specific carry-over issues: The Achilles' heel of ibrutinib TDM

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 D-4, D-5 and C-13(6) 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 D-4, D-5 and C-13(6) 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. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This study focuses on the differential adsorption behavior of ibrutinib and its isotopically labeled analogues in liquid chromatography-tandem mass spectrometry analysis, revealing a preferential adsorption of the non-labeled compound. The research also highlights the strong affinity of ibrutinib to polymeric surfaces under specific conditions, emphasizing the importance of considering this during sample preparation and analysis. This work opens up a new area for discussion on the use of stable isotope labeled internal standards in LC-MS/MS analysis.