An ultra-high-performance liquid chromatography-tandem mass spectrometric method for the determination of hederacoside C, a drug candidate for respiratory disorder, in rat plasma

Hederacoside C is a principal bioactive pharmaceutical ingredient of Hedera helix leaf extracts. H. helix extracts have long been used in folk medicine for the treatment of respiratory disorders. Currently, hederacoside C is investigated as a promising candidate for the treatment of respiratory diseases. In this study, an accurate, sensitive, rapid, and reliable bioanalytical method was developed for the determination of hederacoside C in rat plasma using ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). For sample preparation, plasma proteins were precipitated with 0.1% acetic acid in acetonitrile. Waters UPLC BEH C-18 (2.1 mm I.D. x 100 mm, 1.7 mu m) column was used for chromatographic separation. A gradient elution of mobile phases consisting of 0.02% acetic acid in distilled water (solvent A) and 0.02% acetic acid in acetonitrile (solvent B) was used at a flow rate of 0.3 mL/min. The multiple reaction monitoring (MRM) mode was used for mass spectrometric detection; the MRM transitions were m/z 1219.7 -> m/z 469.2 for hederacoside C and m/z 1108.3 -> m/z 221.2 for ginsenoside Rb1 (internal standard) in the negative ionization mode. A calibration curve was constructed in the range of 10-1000 ng/mL. The intra- and inter-day precision and accuracy were within 5%. The developed UPLC-MS/MS method was successfully applied in a pharmacokinetic study of hederacoside C in rats. Hederacoside C was quickly but inadequately absorbed from the gastrointestinal tract of rats resulting in extremely low bioavailability and relatively slow clearance. (C) 2016 Elsevier B.V. All rights reserved.This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry (NRF-2014R1A1A1A05002840)