The Effect of Acupoint Application of Sinomenine for Rheumatoid Arthritis Measured by Microdialysis and UPLC-MS/MS

Abstract

Objective. This study aimed to investigate the treatment effects of acupoint application of sinomenine in rheumatoid arthritis (RA). RA models were constructed using male New Zealand rabbits. Methods. The rabbits were randomly divided into a blank control group and four experimental groups as follows: ST 36 group (acupoint application of sinomenine at Zusanli); GB 34 group (acupoint application of sinomenine at Yanglingquan); knee-joint group (application directly at the site of the knee joint); and oral administration group (sinomenine administered by gavage). In all rabbits, microdialysis was applied at the knee joint to obtain samples. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters were measured by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the PK/PD models were established according to the parameters derived. Results. Sinomenine concentration was in the range of 0.832–208 ng/mL, and the peak area showed a good linear relationship with the regression equation of y = 539.64x + 953.81; r = 0.9998. Moreover, good specificity and precision were obtained for the LC-MS/MS method of sinomenine evaluation in the microdialysate samples. The PK analysis showed that the sinomenine effect time was longer in the ST 36 group (area under the time-concentration curve (AUC): 12683.81 h·ng/ml and Tmax: 6.21 h) than in the other groups. Arginine and citrulline were selected as the indices for PD, and in the analysis of parameters for PK/PD, the highest value of Emax and the lowest value of ke0 were obtained in the ST 36 group. Conclusion. Acupoint application of sinomenine at ST 36 has potential for use in patients with RA by enabling enhanced and prolonged treatment effects.