Bioanalytische LC-MS/MS procedures en hun toepassingen in preklinische farmacokinetische studies van geselecteerde opiaten en nieuwe antikankermiddelen

Abstract

The main aim of this thesis was to develop and validate LC-MS/MS methods for determination of drug concentrations as well as their relevant metabolites in order to support preclinical PK studies of novel and existing drugs in mice. LC-MS/MS methods were developed for the quantification of morphine and its main metabolites, for ibogaine and its main metabolites, for cintirorgon, and for entospletinib and lanraplenib. The preclinical PK studies in mice where these LC-MS/MS method were developed for, were performed to elucidate the role of drug transporters and metabolic enzymes in the disposition of the mentioned drugs that are currently used or are intended for future use to improve treatment against cancer.