A Study On Arsenic Analysis And Its Application To Safety Reevaluation Of Liushenwan

Liushenwan is a famous Tranditional Chinese Medicine(TCM). It comprises realgar, which contains arsenic and has bad effect in people's health. The former safety evaluation of Liushenwan was based on clinic experience and lack of experimental data. In present dissertation, the theory of chemomics was combined with pharmacological and toxicological research. Through the analysis of total arsenic and arsenic speciation, the safety reevaluation of Liushenwan was carried out and its chemical substances and action mechanism were disclosed.In the present dissertation, studies of the arsenic analysis was carried out as follows: (1)An easy and reliable method for the determination of total arsenic in traditional chinese medicine, plasma and tissues was developed by electro heating digestion and ICP-MS determination. (2)An HPLC-ICP-MS method was developed for the speciation analysis of arsenite(Asâ…¢), arsenate(Asâ…¤), monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) in traditional chinese medicine. (3) An HPLC-ICP-MS method was established for the first time for the simultaneous determination of arsenite(Asâ…¢), arsenate(Asâ…¤), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), arsenobetaine (AsB) and arsenocholine (AsC) in plasma and tissues, by using a single anion exchange column and isocratic elution condition.In the second part of present dissertation, the theory of Chemomics was combined with pharmacological and toxicological research. The safety reevaluation of TCM Liushenwan and realgar was carried out based on the hyphenated techniques developed above. The main achievements obtained in this research are: (1)Solvable arsenic contents in Liushenwan were found lower than that in realgar after leached with deionized water, artificial stomach fluid and artificial intestinal fluid, respectively. Contents of solvable arsenic in realgar mixed with components in Liushenwan were lower than those in realgar. It was indicated that components in Liushenwan can reduce solubility of arsenic in realgar, which may decrease toxicity of realgar. (2)Toxicokinetics of beagle dogs after oral administration of Liushenwan and realgar were studied through determination of total arsenic in plasma and arsenic speciation of plasma at Tmax point of toxicokinetic curve. The results showed that, after compatible application of realgar to be Liushenwan, arsenic in plasma could be cleared more easily and transformed to less toxic arsenic species. (3)Tissue distribution of total arsenic in mice given a single oral administration of Liushenwan were studied. Tissue concentrations of total arsenic and arsenic species of beagle dogs given oral administration of Liushenwan and realgar of different dosages after dosing period (28 days) and recovery period (14 days) were investigated. The results are helpful in the safety reevaluation of TCM Liushenwan and medicinal material realgar and of great importance in clinic research. The conception which combines chemomics with pharmacological and toxicological research is essential and provides demonstration for the safety evaluation of TCM.