Naslov
Simultaneous analysis of mitotane and its main metabolites in human blood and urine samples by SPE-HPLC technique

Autori
Mornar, Ana ; Sertić, Miranda ; Turk, Nikša ; Nigović, Biljana ; Koršić, Mirko

Izvornik
Biomedical chromatography (0269-3879) 26 (2012), 11; 1308-1314

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
mitotane; metabolites; SPE-HPLC; RT-PCR; CYP450

Sažetak
Adrenocortical carcinoma (ACC) is a rare malignancy with an incompletely understood pathogenesis and a poor prognosis. The adrenalytic activity of mitotane has made it most important single drug in the treatment of ACC. Unfortunately, the exact mechanism of mitotane action is still unknown. It is believed that mitotane belongs to the class of drugs that require metabolic transformation by cytochrome P450 for therapeutic action ; therefore determination plasma levels of not only mitotane but also its metabolites would help in carrying out the treatment. The objective of this work was to develop and validate SPE-HPLC method for simultaneously determination of mitotane and its metabolites in different biological fluids. The sample preparation consisted of a solid-phase extraction on a Discovery DSC-18 cartridge, while analysis of extracts was performed on a Symmetry C18 column. Usefulness of the proposed method has been confirmed by analysis of plasma, red cell and urine samples from patient chronically treated with 1.5 g of mitotane. The patient involved in this study had high plasma concentration of mitotane and none of investigated metabolites was found. In order to investigate weather the polymorphism of CYP2C9 and CYP2C19 enzymes could be related to the metabolism of mitotane RT-PCR analysis was performed.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA