Determination of nine components of fried Ziziphi Spinosae Semen extract in beagle dog plasma by UPLC-MS/MS and its application in pharmacokinetic research
This study established a convenient,rapid,and sensitive ultra-performance liquid chromatography tandem mass spec-trometry(UPLC-MS/MS)method for simultaneous determination of magnoflorine,(R)-coclaurine,vicenin Ⅱ,isospinosin,spinosin,swertisin,N-nornuciferine,6‴-feruloylspinosin,and jujuboside B in beagle dog plasma after oral administration of fried Ziziphi Spi-nosae Semen(FZSS)extract.The Waters HSS-T3 C18 column(2.1 mm×100 mm,1.8 μm)was used.The methanol-aqueous solu-tion(containing 0.01%formic acid)was adopted as the mobile phase for gradient elution.The nine components and two internal standards were completely separated within 8 min.The mass spectrometry detection was performed in multiple reaction monitoring(MRM)mode by positive and negative ion switching of electrospray ionization.The analytical method was validated in terms of speci-ficity,selectivity,linear range,accuracy,precision,recovery,matrix effect,and stability.It could meet the requirement of pharmaco-kinetic research after oral administration of FZSS extract to beagle dogs.The results showed that the time to reach the peak concentra-tion(Tmax)of magnoflorine,(R)-coclaurine,vicenin Ⅱ,isospinosin,spinosin,6‴-feruloylspinosin,and jujuboside B was 2.40-3.20 h,and the elimination halflife(t1/2)was 2.08-6.79 h after a single-dose oral administration of FZSS to beagle dogs.The exposure of magnoflorine and spinosin was high,with a peak concentration(Cmax)of 76.7 and 31.5 ng·mL-1 and an area under the curve(AUC0-∞)of 581 and 315 ng·h·mL-1,respectively.The exposure of the remaining five compounds was lower,with a Cmax of 0.81-13.0 ng·mL-1 and an AUC0-∞ of 6.00-106 ng·h·mL-1.This study provides a reference for the follow-up research of FZSS.
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