Abstract

A new, rapid, and sensitive gas chromatography--mass spectrometry (GC-MS) method was developed for the determination of ezetimibe (EZE) in human plasma. EZE was derivatized prior to GC-MS analysis. Various derivatization techniques such as acetylation, methylation, and silylation were tried. EZE was extracted from plasma with high recovery (94.39%--97.57%) using methyl tertbutyl ether and carbonate buffer (pH 9). Chromatographic conditions were optimized using chemometric methods. In the first step, optimization with factorial design, chromatographic variables (initial and final column temperature, oven ramp rate, and flow rate of gas) were screened to select important variables for the retention of EZE. In the second step, central composite design was applied to decide on the retention time of EZE. The analysis was achieved in a short period of time (

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