Objective:A chiral resolution method for enantiomers of two chiral nitrogen-containing metabolites R-gentiandiol and S-gentiandiol of swertiamarin in plasma was developed,and the pharmacokinetics of the metabolites we...Objective:A chiral resolution method for enantiomers of two chiral nitrogen-containing metabolites R-gentiandiol and S-gentiandiol of swertiamarin in plasma was developed,and the pharmacokinetics of the metabolites were studied.Methods:The metabolites of swertiamarin in vivo were detected by LC-MS/MS using Astec CyclobondⅡCyclodextrin column(4.6 mm×100 mm,5μm),gradient elution with acetonitrile-water as mobile phase,and monitored by multiple reaction monitoring(MRM)method in positive mode.The ion pairs for quantitative analysis are R-gentiandiol(m/z 210.04→192.06),S-gentiandiol(m/z 210.04→192.06)and gentianone(m/z 192.02→162.08).Results:The linear correlation coefficients of the method developed were greater than 0.999,the precision was less than 7.00%,the recovery was 99.57%-102.65%,and the matrix effect was 90.94%-91.34%.The peak t_(max)of R-gentiandiol and S-gentiandiol in rat plasma after oral administration of swertiamarin were(1.63±0.23)h and(1.58±0.21)h,t_(1/2)was(6.23±0.52)h and(5.46±0.38)h,C_(max)was(86.79±20.81)ng/mL and(60.72±18.95)ng/mL,and the AUC_(0-24)were(1094.58±86.37))(ng·h)/mL and(724.67±58.38)(ng·h)/mL,respectively.Conclusion:The method was highly sensitive with good accuracy and precision,and it was successfully applied for chiral resolution and pharmacokinetics study of R-gentiandiol and S-gentiandiol in plasma.The method developed and experimental results will provide scientific basis for the study of pharmacodynamics and pharmacodynamic material basis of swertiamarin,and lay a foundation for clinical application and resource development of TCM monomer.展开更多
基金This study was supported by Key Research and Development Guidance Program of Heilongjiang Province(GZ20210125)。
文摘Objective:A chiral resolution method for enantiomers of two chiral nitrogen-containing metabolites R-gentiandiol and S-gentiandiol of swertiamarin in plasma was developed,and the pharmacokinetics of the metabolites were studied.Methods:The metabolites of swertiamarin in vivo were detected by LC-MS/MS using Astec CyclobondⅡCyclodextrin column(4.6 mm×100 mm,5μm),gradient elution with acetonitrile-water as mobile phase,and monitored by multiple reaction monitoring(MRM)method in positive mode.The ion pairs for quantitative analysis are R-gentiandiol(m/z 210.04→192.06),S-gentiandiol(m/z 210.04→192.06)and gentianone(m/z 192.02→162.08).Results:The linear correlation coefficients of the method developed were greater than 0.999,the precision was less than 7.00%,the recovery was 99.57%-102.65%,and the matrix effect was 90.94%-91.34%.The peak t_(max)of R-gentiandiol and S-gentiandiol in rat plasma after oral administration of swertiamarin were(1.63±0.23)h and(1.58±0.21)h,t_(1/2)was(6.23±0.52)h and(5.46±0.38)h,C_(max)was(86.79±20.81)ng/mL and(60.72±18.95)ng/mL,and the AUC_(0-24)were(1094.58±86.37))(ng·h)/mL and(724.67±58.38)(ng·h)/mL,respectively.Conclusion:The method was highly sensitive with good accuracy and precision,and it was successfully applied for chiral resolution and pharmacokinetics study of R-gentiandiol and S-gentiandiol in plasma.The method developed and experimental results will provide scientific basis for the study of pharmacodynamics and pharmacodynamic material basis of swertiamarin,and lay a foundation for clinical application and resource development of TCM monomer.
