Quantitative analysis of five components of Sargentodoxae caulis-Radix alangii drug pair using UPLC-MS/MS in rat plasma and RAW264.7 cells for comparative pharmacokinetics in normal and diseased states.

内容摘要

The Sargentodoxae caulis-Radix alangii (SR) drug pair has been traditionally used by the Hmong for treating rheumatoid arthritis (RA). However, its pharmacokinetic behavior under disease conditions remains largely unexplored. To address this gap, a UPLC-MS/MS method was established to determine the concentrations of salidroside, loganate, vanillic acid, anabasine, and protocatechuic acid, key bioactive components of SR in rat plasma and RAW264.7 cells. This method aimed to investigate the effects of disease states on the pharmacokinetic profiles of these components both in vitro and in vivo. The components were detected using multiple reaction monitoring (MRM) in both positive and negative ion modes. Each calibration curve exhibited a high correlation coefficient (R2 > 0.99). The intra-and inter-day precisions for these analyses were all below 15%, with accuracy ranging from 85% to 115%. The relative standard deviation (RSD) values for stability, recovery, matrix effect, and reproducibility remained below 15.0%. This method was successfully applied to investigate the pharmacokinetics of these components in rat plasma and RAW264.7 cells after administration of SR. In rat pharmacokinetic experiments, significant differences were observed in the AUC(0-t), MRT(0-t), and Clz/F values of salidroside, loganate, vanillic acid, anabasine, and protocatechuic acid between adjuvant-induced arthritis (AA) rats and normal rats. In cellular pharmacokinetic experiments, compared to the normal group, the AUC(0-t) and MRT(0-t) of these components were increased in the LPS-induced inflammatory cell model, while Clz/F was decreased, consistent with the in vivo findings. These results suggest that the absorption rate of these components in SR was enhanced in AA rats and inflammatory cells, while their elimination rate was reduced. This indicates a potential alteration in the rate and extent of drug metabolism. This study provides a theoretical reference for further clarifying the pharmacodynamic basis of SR, particularly in the context of inflammatory conditions. Future research should focus on elucidating the specific mechanisms underlying these pharmacokinetic changes and exploring their clinical implications.