Simultaneous determination of cimicifugoside H-2, cimicifugoside H-1, 23-epi-26-deoxyactein, cimigenol xyloside and 25-O-acetylcimigenoside in beagle dog plasma by LC–MS/MS

A selective and sensitive LC–MS/MS method was developed and validated for the simultaneous determination of five constituents (cimicifugoside H-2, cimicifugoside H-1, 23-epi-26-deoxyactein, cimigenol xyloside and 25-O-acetylcimigenoside) of Cimicifuga foetida L. in beagle dog plasma. The quantitation was performed on a LC–MS/MS with negative electrospray ionization in selected reaction monitoring (SRM) mode. A gradient mobile phase composed of methanol and water was used at a flow rate of 0.4 ml/min. All the analytes and internal standard (20 (S)-ginsenoside Rg3) were isolated from plasma samples by a liquid–liquid extraction method. The average extraction recoveries were 73–74% for cimicifugoside H-2, 89–94% for cimicifugoside H-1, 73–80% for 23-epi-26-deoxyactein, 89–91% for cimigenol xyloside, 87–96% for 25-O-acetylcimigenoside, respectively. The method showed good linearity and no endogenous material interfered with all the five compounds and I.S. peaks. The lower limit of quantification (LLOQ) of all analytes was 0.5 ng/ml. The intra- and inter-day precision of analysis was less than 15% for each analyte at concentrations of 2.0, 50, 500 ng/ml, and the accuracy ranged from 85.8% to 107%. This method was successfully applied to reveal the pharmacokinetic properties of cimicifugoside H-2, cimicifugoside H-1, 23-epi-26-deoxyactein, cimigenol xyloside and 25-O-acetylcimigenoside after oral administration.

► First LC-MS/MS procedure for the simultaneous determination of five saponins from Cimicifuga foetida L. in beagle dog plasma. ► The method was validated according to most international and journal standards. ► The pharmacokinetics of these compounds in beagle dogs given in this manuscript was reported for the first time. ► This study will be instrumental for future clinical pharmacokinetics studies on the extracts of C. foetida.