Pharmacokinetics of Sijunzi decoction in rat plasma after oral administration using ultra-high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry.

Abstract

Sijunzi decoction (SJZD) is one of the most well-known traditional Chinese herbal formulations. This study elucidates the pharmacokinetics of SJZD in rat plasma after the administration of a single oral dose of 3 mL/kg using ultra-high-performance liquid chromatography electrospray ionization quadrupole-time of flight mass spectrometry (UHPLC-ESI-Q-TOF/MS) with bergapten as an internal standard. The separation was performed on an Agilent Zorbax Eclipse Plus C18 column (2.1 × 50 mm, 1.8 μm) by elution with acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.3 mL/min. Electrospray ionization in positive and negative ion modes was used to quantify six compounds, with monitored ion m/z values of 249.1397 [M + H]+ and 529.3857 [M + H]+ for atractylenolide III (ATL-III) and pachymic acid (PA), respectively, and m/z of 1107.6638 [M - H]- , 991.5746 [M - H + HCOO]- , 821.3714 [M - H]- , 469.3315 [M - H]- for ginsenoside Rb1, Re, glycyrrhizic acid (GL), and glycyrrhetinic acid (GA), respectively. The calibration curves for ginsenoside Rb1 , Re, ATL-III, PA, GL and GA were 0.0015-0.75, 0.001-0.5, 0.0004-0.2, 0.003-0.9, 0.0015-0.3 and 0.001-1.5 μg/mL, respectively. The intra- and inter-day precisions (RSD) were <14.3%. The rapid, sensitive and specific UHPLC-ESI-Q-TOF/MS method developed and validated in this study was successfully applied to the simultaneous determination of the six components of SJZD using rat plasma for pharmacokinetic studies after oral administration.