A sensitive and selective method for the quantitative analysis of miglitol in rat plasma using unique solid-phase extraction coupled with liquid chromatography–tandem mass spectrometry

A sensitive, selective and robust liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of miglitol in rat plasma. The sample preparation procedures involved protein precipitation and unique solid-phase extraction, which efficiently removed sources of ion suppression and column degradation interference present in the plasma. Chromatographic separation was achieved on an amide column using 10 mmol/L CH3COONH4 and CH3CN:CH3OH (90:10, v/v) as the mobile phase under gradient conditions. Detection was performed using tandem mass spectrometry equipped with an electrospray ionization interface in positive ion mode.The selected reaction monitoring transitions for miglitol and a stable isotope-labeled internal standard were m/z 208  m/z 146 and m/z 212  m/z 176, respectively. The correlation coefficients of the calibration curves ranged from 0.9984 to 0.9993 over a concentration range of 0.5–100 ng/mL plasma. The quantification limit of the proposed method was more than 10 times lower than those of previously reported LC-MS/MS methods. The novel method was successfully validated and applied to a pharmacokinetic study in rats. Copyright © 2014 John Wiley & Sons, Ltd.