Analysis of sibutramine metabolites as N-trifluoroacetamide and O-trimethylsilyl derivatives by gas chromatography-mass spectrometry in urine.
A method for identifying the metabolites of sibutramine 1-(4(chlorophenyl)-N,N-dimethyl-alpha-(2-methylpropyl))cyclobutanemethanamine) in urine, utilizing a double derivatization strategy, with N-methyl-N-(trimethylsilyl)-trifluoroacetamide and N-methyl-bis-(trifluoroacetamide), in gas chromatography/mass spectrometry is proposed. This methodology results in mass spectra with at least three fragments in abundance superior to 20%, attending the World Anti-Doping Agency identification criteria for qualitative assays. The characterization of the derivatives was obtained through two ionization modes: Chemical Ionization and Electron Impact ionization, both in full scan mode. Sibutramine was administered to 5 (five) volunteers and the excretion profile followed for 92h. Routine analytical, hydroxy-cyclobutane-bis-nor-sibutramine which becomes the more abundant metabolite in the first 10h and hydroxy-isopropyl-bis-nor-sibutramine which becomes the most abundant after 40h, were proposed for doping monitoring.
Sardela
V F
VF
Universidade Federal do Rio de Janeiro, Instituto de Química, Ilha do Fundão, Avenida Athos da Silveira Ramos, 149, 21941-909, LAB DOP-LADETEC, Rio de Janeiro, RJ, Brazil.
Motta
M T R
MT
Padilha
M C
MC
Pereira
H M G
HM
Neto
F R Aquino
FR
D000081:Acetamides; D003503:Cyclobutanes / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D004300:Doping in Sports; D004355:Drug Stability; D005260:Female; D005463:Fluoroacetates; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014269:Trifluoroacetic Acid / Q000652:urine; D014297:Trimethylsilyl Compounds / Q000652:urine*
D000081:Acetamides; D003503:Cyclobutanes; D005463:Fluoroacetates; D014297:Trimethylsilyl Compounds; C030688:trifluoroacetamide; D014269:Trifluoroacetic Acid; C058254:sibutramine