Simultaneous Determination of Three Organic Acids of Anshen Buxin Liuwei Pills in Rat Plasma Using LC-MS/MS and Pharmacokinetic Study
OBJECTIVE To establish a liquid chromatography tandem mass spectrometry(LC-MS/MS)method for determination of cinnamic acid(CA),vanillic acid(VA)and 3,3'-O-dimethylellagic acid(DMA)concentrations in rat plasma and evaluate the pharmacokinetics and the correlations between dose and systemic exposure levels of CA,VA and DMA in rats after single dose administration of Anshen Buxin Liuwei Pills(ASBX).METHODS Blood was collected from male SD rats at different time points after different dose administration.The plasma was processed by protein precipitation method.The concentrations of CA,VA and DMA in plasma were determined by LC-MS/MS method.Pharmacokinetic parameters were calculated with MaS Studio software.The correlations between dose and systemic exposure level were analyzed by confidence interval method.RESULTS The linear relationship of the calibration curves of the three compounds were good within the tested ranges,and the specificity,precision and accuracy,recovery,matrix effect and stability of the method all met the requirements for biological sample assay.After single intragastric administration of ASBX,the tmax of CA,VA and DMA were 0.22-0.40,0.08 and 5.40-8.20 h,the t1/2 were 0.79-2.04,0.37-0.65 and 4.26-9.58 h,the ρmax were 279.70-302.88,16.42-43.33,and 2.81-7.20 ng·mL-1,and the AUC0-∞ were 351.83-537.96,7.20-18.82,and 29.27-119.64 ng·h·mL-1,respectively.The results of confidence interval analysis showed that the ρmax and AUC of VA and DMA,and AUC of CA were positively correlated with dose,but theρma,of CA was not clearly correlated with dose.CONCLUSION The LC-MS/MS analysis method is proved to be rapid,sensitive,and accurate,so it can be applied to the pharmacokinetic study of ASBX after intragastric administration in rats.This sdtudy provides a reference for future research on the pharmacodynamic material basis and safe and effective clinical use of ASBX.
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