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Application of LC-MS/MS methods to in vitro transport experiments
Salvová, Šárka ; Váňová, Nela (advisor) ; Kastner, Petr (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department: Deparrment of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Šárka Salvová Supervisor: PharmDr. Nela Váňová, Ph.D. Title of Thesis: Application of LC-MS/MS methods to in vitro transport experiments Gilteritinib, an antineoplastic drug, is used for targeted anticancer therapy. It belongs to the group of receptor tyrosine kinase inhibitors. Its structure is based on a pyrazinecarboxamide skeleton. So far, it has been chromatographically determined in biological material only from plasma. In this diploma thesis, gilteritinib was analyzed from Opti-MEM cell medium to be used in vitro transport experiments. Subsequently the LC-MS/MS method was optimized and validated. During progression and optimization of the LS-MS/MS method, the Thermo Finnigan LCQ Advantage Max Ion Trap was observed that with an increasing number of injections had been shown increasing signal suppression for gilteritinib and its internal standard (maraviroc), which reached up to 75 % after only 30 sprays. Contamination of the inlet to the ion transfer capillary, to which the ion source (electrospray) is placed diagonally, was also visible. Thereafter it was tested whether another construction of the ion source (orthogonal position of electrospray)...
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