Simultaneous Determination and Pharmacokinetics of Tetrandrine,Fangchinoline,and Cyclanoline in Rat Plasma by Ultra-High Performance Liquid Chromatography-Mass Spectrometry after Oral Administration of Stephaniae Tetrandrae Radix Extract

Objective:The objective of the study was to develop a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of tetrandrine,fangchinoline,and cyclanoline in rat plasma and to investigate their pharmacokinetics after oral administration of Stephaniae Tetrandrae Radix extracts.Methods:Sample pretreatment involved methanol pretreatment and liquid–liquid extraction of ethyl acetate from plasma with methanol.Tramadol was used as the internal standard.The analysis was performed using an high strength silica T3 column(100 mm×2.1 mm,1.8μm)and a gradient elution method consisting of mobile phase solution A(0.1%formic acid in water)and B(acetonitrile)at a flow rate of 0.4 mL/min.The detection was performed using a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode and using an electrospray ionization source in the positive ionization mode.Results:High efficiency was achieved with an analysis time of 4 min/sample.The calibration curve linear in the concentration range of 1250 ng/ml(R^(2)≥0.9900)and the lower limit of quantification is 1 ng/ml.The intraday and interday precision(relative standard deviation)values were lower than 9.4.Accuracy(relative error)was within 10.3%at all three quality control levels.Conclusions:This method was successfully applied in pharmacokinetics of tetrandrine,fangchinoline,and cyclanoline in rats after oral administration of Stephaniae Tetrandrae Radix extracts.The maximum plasma concentration(C_(max))of tetrandrine,fangchinoline,and cyclanoline was 124.71±16.08,84.56±3.28,and 57.61±6.26 ng/mL,respectively.The time to reach C_(max)was 10.39±3.04 for tetrandrine,10.17±3.04 for fangchinoline,and 6.40±3.16 for cyclanoline.The pharmacokinetic results might help further guide the clinical application of Stephaniae Tetrandrae Radix.

Research Progress on Pharmacological Action and Clinical Application of Stephania Tetrandrae Radix

Stephania Tetrandrae Radix is one of the common traditional Chinese medicines,which has bitter and pungent taste as well as cold properties. It can subside edema,get rid of rheumatism and relieve pain. Therefore,it is mainly used for the treatment of rheumatism arthralgia,edema,dysuria,athlete's foot,swollen wet sores and other diseases in traditional Chinese medicine( TCM). Stephania Tetrandrae Radix is mainly composed of dual-benzyl isoquinoline alkaloids,including tetrandrine,fangchinoline and so on. Modern pharmacology research shows that Stephania Tetrandrae Radix and its main components have a wide range of pharmacological activity in the anti-inflammatory,anti-pathogenic microorganisms,anti-tumor,anti-hypertension,anti-arrhythmia,anti-myocardial ischemia,anti-fibrosis,anti-silicosis,inhibiting scar and other aspects,with broad application prospect. Stephania Tetrandrae Radix is often applied with compatibility of other Chinese medicines in clinically,and has achieved obvious effects in the treatment of rheumatoid arthritis,cardiovascular disease,cancer,hypertension,liver ascites and other diseases. There are some representative prescriptions,such as Fangji Fuling decoction,Fangji Huangqi decoction,Jijiao Lihuang pill,Xuanbi decoction,compound Hanfangji granule and so on. In this paper,the pharmacological effects and clinical applications of Stephania Tetrandrae Radix in the past ten years are reviewed,providing the reference for its further development and application.