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Determination of Sibutramine and Its N-Desmethyl Metabolites in Human Plasma Using HPLC Coupled with Tandem Mass Spectroscopy

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A sensitive and selective liquid chromatographic method coupled with tandem mass spectrometry has been developed and validated for the determination of Sibutramine and its N-desmethyl metabolites in human plasma. The analytes Sibutramine, N-monodesmethylsibutramine, N-N-didesmethylsibutramine and Bisoprolol (internal standard) have been separated on a reversed phase column (Merck, Purospher RP-C18, 30 × 4.0 (mm), 3 μm) using a mobile phase which consists of an aqueous solution 20 mM ammonium acetate pH 4.0 (adjustment by acetic acid) in water and acetonitrile (67:33 v/v (%)), flow rate 0.40 (mL/min). Detection has utilized a tandem MS/MS and the analytes have been ionized using an ESI source in the positive ion mode prior to detection by Multiple Reaction Monitoring (MRM) mode. The analytes were monitored at the following transitions (m/z) 280.20 → 125.20 for Sibutramine, (m/z) 268.10 → 126.9 and 268.10 → 141.00 for N-monodesmethylsibutramine, (m/z) 254.10 → 126.9 and 254.10 → 141.00 for N-N-didesmethylsibutramine and (m/z) 2326.20 → 107.10 for Bisoprolol respectively. Sibutramine, N-monodesmethylsibutramine and N-N-didesmethylsibutramine linearity were demonstrated over the concentrations ranging from 0.10 to 11.00 (ng/mL). The developed method has been fully validated.
Cite this paper
Al-Bayari, M. (2014) Determination of Sibutramine and Its N-Desmethyl Metabolites in Human Plasma Using HPLC Coupled with Tandem Mass Spectroscopy. American Journal of Analytical Chemistry, 5, 589-597. doi: 10.4236/ajac.2014.59066. 
 

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http://dx.doi.org/10.1016/S0731-7085(99)00303-9           eww141110lx
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