Simultaneous determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re and 20(S) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a Panax notoginseng saponin preparation

•The saponins (R1, Rg1, and Re) and their sapogenin (PPT) were determined simultaneously for the first time by UPLC–MS/MS.•The analytes were detected without interference in Selected Reaction Monitoring mode with electrospray ionization change from positive to negative.•The determination of this saponins in the presence of the aglycone PPT in plasma considered quite original, and for the first time, we quantified PPT as a metabolite in a pharmacokinetic study.

20(S) protopanaxatriol is the main metabolite of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re in Panax notoginseng and has significant activities. A ultra high performance liquid mass spectrometry method has been developed and validated for the simultaneous determination of notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), ginsenoside Re (Re) and 20(S) protopanaxatriol (PPT) in beagle dog plasma after oral administration of a Panax notoginseng saponin preparation. After the addition of the internal standard (digoxin), plasma samples were subjected to liquid–liquid extraction with acetone and methanol and separated on a 100 × 2.1 mm ACQUITY 1.7 μm C18 column (Waters, USA), with acetonitrile and water as the mobile phase, within a runtime of 7.0 min. The analytes were detected without interference in Selected Reaction Monitoring mode with a change in the electrospray ionization from positive to negative. The detection limits were 0.01 to 0.04 mg/L and the calibration curves of the peak areas for the four ingredients were linear over four orders of magnitude with a correlation coefficient greater than 0.9957. The intra-day and inter-day precision values (relative standard deviation, RSD, %) were within 10.25% and 13.51%, respectively, and the accuracy (relative error, RE, %) was less than 7.81%. The validated method was successfully applied to a comparative pharmacokinetic study of four saponins in beagle dogs after oral administration of a Panax Notoginseng Saponins preparation. The pharmacokinetic parameters were calculated with DAS 3.20. The Tmax and Cmax values indicate a dose–dose relationship between the saponins (R1, Rg1, and Re) and their sapogenin (PPT).