Study On Determination Method And Pharmacokinetics And Distributions Of Aristolochic Acid A In Animals

In recent years, the nephrotoxicity of some Chinese herbs that contain Aristolochic acids has been reported. There are many Aristolochic acids, in which Aristolochic acid A is the major component and is mostly related to the nephrotoxicity. In this study, the determination method for Aristolochic acid A in biological samples has been developed. The pharmacokinetics of Aristolochic acid A and its distributions in animals have been studied. The results of this study can provide the reference for further study.For the purpose to establish the determination method for Aristolochic acid A in biological samples, the preparation of the biological samples is expressed as follow: Aristolochic acid A is extracted with methanol from the samples by two times, after centrifuging, the solvent are evaporated at 60 °C and the residue is dissolved with a small volume mobile phase. The solution is submitted to HPLC which describ as follow after centrifuging.The ion-suppression chromatography is introduced in this paper to determinate Aristolochic acid A. Compounds are separated on a C₁₈ column eluted with a gradient of methanol and 20mmol/L ammonium acetate and acetic acid (pH 5.5) solution. The detection wavelength is 316 nm and the UV spectrum is acquired as well by DAD. Naproxen is used as internal standard.The method proposed is used for analysis Aristolochic acid A in plasma, heart, liver, lung, kidney samples. This method is evaluated by linearity, extractive recovery, analytical recovery, within-day and between-day precision.The method is sensitive, accurate, precise and reproducible, and suitable for clinical diagnosis , forensic identification and further study of Aristolochic acid A in vivo.The pharmacokinetics of Aristolochic acid A is investigated in 5 healthy rats after oral administration of 50mg/kg. Blood samples are collected at different intervals after drug administration, and the concentration-time curves are acquired. The result shows that the pharmacokineics of Aristolochic acid A could be fitted to two-compartment model in rats and the weight is 1/C/C.The distributions of Aristolochic acid A in mouse are also investigated. The result shows that the quantity of drug in kidney is more than that in other tissues.The method for Aristolochic acid A in biological samples is established in this paper. The pharmacokinetics and distributions of Aristolochic acid A are also studied. The results can provide a valuable method and reference for clinical diagnosis, forensic identification and further study.