Determination and validation of chikusetsusaponin IVa in rat plasma by UPLC-MS/MS and its application to pharmacokinetic study

• Published in: Biomedical chromatography 2016-09, Vol.30 (9), p.1423-1429
• Main Authors: Wang, Ying, Liu, Shi-Ping, Guo, Mei-Hua, Wang, Zhuo
• Format: Article
• Language: English
• Subjects: Animals; Biological Availability; chikusetsusaponin IVa; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - blood; Oleanolic Acid - pharmacokinetics; pharmacokinetics; rat plasma; Rats; Saponins - blood; Saponins - pharmacokinetics; Tandem Mass Spectrometry - methods; UPLC-MS/MS
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.3700

A novel, sensitive and rapid ultra‐performance liquid chromatography–tandem mass spectrometric method for the quantification of chikusetsusaponin IVa (CHS‐IVa) in rat plasma was established and validated. Plasma samples were pre‐treated by precipitation of protein with acetonitrile and chromatographed on a Waters Symmetry C18 analytical column (4.6 × 50 mm, i.d., 3.5 μm) using a mobile phase consisting of methanol and water containing 0.05% formic acid (55:45, v/v) at a flow rate of 0.4 mL/min. The deprotonated molecular ions [M − H]– were employed in electrospray negative ionization mode and selected reaction monitoring transitions were performed for detection. The calibration curves exhibited good linearity (r > 0.99) over the range of 0.5–1000 ng/mL for CHS‐IVa. The recoveries of CHS‐IVa were >92.5% and exhibited no severe matrix effect. This method was successfully applied in the pharmacokinetic study of CHS‐IVa in rats. For oral administration, the plasma concentrations of CHS‐IVa increased to a peak value at 0.35 ± 0.14 h, followed by a gradual decrease to the lower limit of quantitation in 24 h. For intravenous administration, the plasma concentrations of CHS‐IVa decreased quickly (t1/2, 1.59 ± 0.25 h). The absolute bioavailability of CHS‐IVa in rats was 8.63%. Copyright © 2016 John Wiley & Sons, Ltd.