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Development of LC-MS method for compounds used for determination of cytochrome activity
Smolík, Martin ; Lochman, Lukáš (advisor) ; Horáček, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Bc. Martin Smolík Supervisor: PharmDr. Lukáš Lochman, Ph.D. Consultant: prof. PharmDr. Petr Pávek, Ph.D. Title of thesis: Development of LC-MS method for compounds used for determination of cytochrome activity. Cytochromes P450 (CYP450) are enzymes that play a key role in the metabolism of xenobiotics and some endobiotics (cholesterol, steroid hormones, and eicosanoids). They are present in the liver, gastrointestinal tract, lungs, and kidneys. Determination of CYP450 activity is a valuable tool to detect drug interactions resulting from inhibition or induction of various isoforms of this enzyme. This thesis is devoted to the development and validation of a new analytical method using liquid chromatography coupled with tandem mass spectrometry for the determination of activity CYP450 isoforms 3A4, 2C9, and 2B6, which are crucial for the metabolism of many drugs and biologically active substances. In the framework of this thesis, a new method was developed providing a fast, accurate, and reliable measurement of the activity of these enzymes based on the quantification of specific CYP450 substrates, namely midazolam (3A4), diclofenac (2C9), bupropion (2B6) and their...
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