College of Pharmacy, Kyung-Hee University, Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea.
A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method with electrospray ionization in positive ion multiple reaction monitoring mode was developed for the quantification of mazindol (an anorectic agent) in human plasma. Fluoxetine was adopted as an internal standard (IS), and sample preparation involved one-step liquid/liquid extraction using ethyl acetate. The transition monitored were m/z 285>44 for mazindol and m/z 310>44 for IS. Chromatographic separation was achieved on a Capcell Pak MGII C(18) column using an isocratic mobile phase, consisting of acetonitrile-20mM ammonium formate in water (50:50, v/v, adjusted to pH 3.5 with formic acid) at a flow-rate of 0.2mL/min. The retention times of mazindol and fluoxetine were 1.03min and 1.45min, respectively. The lower limit of quantitation (LLOQ) was 0.1ng/mL using 200microL of plasma, and no interferences were detected in chromatograms. The bench top stability of mazindol was evaluated in buffered and non-buffered plasma. The selectivity, linearity, precision, accuracy, recovery, and stability of the devised method were fully validated and absolute and relative matrix effects were evaluated. The described method provides a fast and sensitive analytical tool for determining mazindol levels in plasma, and was successfully applied to a pharmacokinetic study in 24 healthy human subjects after oral administration of 2mg tablet formulation of mazindol under fasting conditions.
PMID: 19272843 [PubMed - indexed for MEDLINE
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