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Detection of sibutramine administration: a gas chromatography/mass spectrometry study of the main urinary metabolites
Author(s) -
StranoRossi Sabina,
Colamonici Cristiana,
Botrè Francesco
Publication year - 2006
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2807
Subject(s) - chemistry , chromatography , sibutramine , derivatization , metabolite , mass spectrometry , gas chromatography–mass spectrometry , urine , glucuronide , detection limit , gas chromatography , biochemistry , medicine , weight loss , obesity
Abstract A gas chromatographic/mass spectrometric (GC/MS) study aimed at identifying the metabolites of sibutramine (1‐(4‐chlorophenyl)‐ N , N ‐dimethyl‐ α ‐(2‐methylpropyl)cyclobutanemethanamine) in urine is described. Urinary excretion of sibutramine metabolites following the oral administration of a single dose of sibutramine was followed by GC/MS analysis. After identification of the chromatographic signals corresponding to the six main urinary metabolites, the fragmentation pattern was studied in electron ionization (EI) mode after derivatization to the corresponding methyl and trimethylsilyl derivatives. Urine samples were pretreated according to a reference procedure (liquid/liquid separation, enzymatic hydrolysis, pre‐concentration under a stream of nitrogen and derivatization, either under thermal incubation and by microwave irradiation). All sibutramine metabolites were excreted as glucuroconjugates, and retain the chiral carbon present in the sibutramine skeleton. The metabolites identified included mono‐desmethylsibutramine (nor‐sibutramine), bi‐desmethylsibutramine (nor‐nor‐sibutramine), and the corresponding hydroxylated compounds, the hydroxylation taking place either on the cyclobutane or on the isopropyl chain. The excretion profiles of the different metabolites were also evaluated. From an analytical point of view, the method can be applied to different fields of forensic analytical toxicology, including anti‐doping analysis. Although the lack of certified reference materials does not allow a precise determination of the limits of detection (LODs) of all the sibutramine metabolites, an estimation taking into account the response factor of similar compounds ensures that all metabolites are still clearly detectable in a range of concentrations between 10 and 50 ng/mL, thus satisfying the minimum required performance limits (MRPLs) of the World Anti‐Doping Agency (WADA). Copyright © 2006 John Wiley & Sons, Ltd.