In vitro and in vivo metabolism studies of dimethazine.

Autor: Geldof L; Doping Control Laboratory, Ghent University, Technologiepark 30 B, B-9052, Zwijnaarde, Belgium., Tudela E; Doping Control Laboratory, Ghent University, Technologiepark 30 B, B-9052, Zwijnaarde, Belgium., Lootens L; Doping Control Laboratory, Ghent University, Technologiepark 30 B, B-9052, Zwijnaarde, Belgium., van Lysebeth J; Doping Control Laboratory, Ghent University, Technologiepark 30 B, B-9052, Zwijnaarde, Belgium., Meuleman P; Center for Vaccinology, Ghent University and Hospital, De Pintelaan 185, B-9000, Ghent, Belgium., Leroux-Roels G; Center for Vaccinology, Ghent University and Hospital, De Pintelaan 185, B-9000, Ghent, Belgium., van Eenoo P; Doping Control Laboratory, Ghent University, Technologiepark 30 B, B-9052, Zwijnaarde, Belgium., Deventer K; Doping Control Laboratory, Ghent University, Technologiepark 30 B, B-9052, Zwijnaarde, Belgium.
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2016 Aug; Vol. 30 (8), pp. 1202-9. Date of Electronic Publication: 2016 Jan 18.
DOI: 10.1002/bmc.3668
Abstrakt: The use of anabolic steroids is prohibited in sports. Effective control is done by monitoring their metabolites in urine samples collected from athletes. Ethical objections however restrict the use of designer steroids in human administration studies. To overcome these problems alternative in vitro and in vivo models were developed to identify metabolites and to assure a fast response by anti-doping laboratories to evolutions on the steroid market. In this study human liver microsomes and an uPA(+/+) -SCID chimeric mouse model were used to elucidate the metabolism of a steroid product called 'Xtreme DMZ'. This product contains the designer steroid dimethazine (DMZ), which consists of two methasterone molecules linked by an azine group. In the performed stability study, degradation from dimethazine to methasterone was observed. By a combination of LC-High Resolution Mass Spectrometry (HRMS) and GC-MS(/MS) analysis methasterone and six other dimethazine metabolites (M1-M6), which are all methasterone metabolites, could be detected besides the parent compound in both models. The phase II metabolism of dimethazine was also investigated in the mouse urine samples. Only metabolites M1 and M2 were exclusively detected in the glucuro-conjugated fraction; all other compounds were also found in the free fraction. For effective control of DMZ misuse in doping control samples, screening for methasterone and methasterone metabolites should be sufficient. Copyright © 2016 John Wiley & Sons, Ltd.
(Copyright © 2016 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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