In Vitro And In Vivo Studies On The Safety Of Arsenic And Mercury Containing Traditional Chinese Medicine-Angong Niuhuang Pills

Objective:Angong Niuhuang Pills(ANP),a famous first-aid traditional Chinese medicine(TCM)prescription,has significant clinical effects on fervescence and stroke induced coma.Cinnabar(HgS)and Realgar(As2S2)were the efficacy components of ANP,which contain heavy metal elements of mercury and arsenic,and is harmful for health by long-term medication.The safety of realgar and cinnabar containing TCMs has aroused great concerns among the public due to the adverse effects frequently reported.Therefore,this study will evaluate the safety of ANP in vitro and in vivo to provide references for clinical drug safety.Methods:Total arsenic and mercury in difference kinds of ANP were determined by a sensitive hydride-generation atomic fluorescence spectrometric(HG-AFS)method after wet digestion.The bioaccessible arsenic and mercury in ANP were extracted by simulated gastric fluids(SGF)and simulated intestinal fluids(SIF)and determined by HG-AFS.Pharmacokinetic and excretory studies were conducted in rats after single oral gavage of ANP,realgar and cinnabar by low and high doses,respectively.Total arsenic and mercury in rat whole blood and urine were determined by HG-AFS after wet digestion.Results:The contents of total arsenic,total mercury,soluble arsenic and soluble mercury in seven difference kinds of ANP were 39.07～44.87 mg/g、15.05～39.92 mg/g、0.4189～1.335 mg/g and 5.04～8.46μg/g,respectively.After single oral administration of high-dose ANP,rat blood arsenic contents,as well as Cmax and AUC were all significantly lower than the corresponding realgar group.However,the blood mercury contents,Cmax and AUC were significantly increased after administration to high dose of ANP in comparison with the corresponding cinnabar group.The total arsenic urinary excretion of ANP group within 24 h was higher than the realgar group,and its total mercury urinary excretion within 24 h was lower than the corresponding cinnabar group,which showed significant differences in high dose.Conclusion:Chinese Pharmacopoeia should improve the quality standards for realgar and cinnabar containing TCMs.More specific and a sensitive test items should be added for the determination of total and soluble amount of arsenic and mercury to ensure the consistency of drug quality.Long-term administration of ANP may pose risks of mercury accumulation.However,the absorption of arsenic is much higher than mercury,clinical attention should be paid to the adverse effects caused by realgar.