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

Abstract

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-C18 (2.1 mm× 150 mm, 5 μm) 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.