Application of a liquid chromatography-tandem mass spectrometry method to the pharmacokinetics, bioavailability and tissue distribution of neohesperidin dihydrochalcone in rats

1. This study was aimed at developing a high sensitive and selective liquid chromatography-tandem mass spectrometry method to quantify neohesperidin dihydrochalcone (NHDC) in rat plasma and tissues for pharmacokinetic, bioavailability and tissue distribution studies. 2. Biological samples were processed with one-step protein precipitation. Rutin was chosen as the internal standard (IS). Chromatographical separation was achieved on an SB-C-18 (2.1mm x 150 mm, 5 mu m) column with acetonitrile-0.1% formic acid in water as the mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in negative ion mode; selected ion monitoring mode was used for quantification using target fragment ions m/z 611.4 for NHDC and m/z 609.1 for IS. 3. Calibration plots were linear over the range of 10-3000 ng/mL for NHDC. Lower limit of quantification (LLOQ) for NHDC was 10 ng/mL. Mean recovery of NHDC from plasma and tissues was better than 80.3%. Coefficient of variation of intra-day and inter-day precision were both less than 15%. The bioavailability of NHDC was 21.8%. 4. In conclusion, a sensitive, simple and specific LC-ESI-MS method for the determination of NHDC in rat biological samples was developed. This developed method is successfully used in the pharmacokinetic and tissue distribution study of NHDC in rats.