Studies On Quality Control And Stability Of Baicalin-zinc(HBZn)

[Objectives]To synthesize Baicalin - zinc(HBZn ),and make a further verification of the structure.To explore a method for the determination of HBZn,and make a primary control of its quality.To study the stability of HBZn by experiments initially. Not only to provide the evidence for establishing quality standards,storage conditions, the period of validity for HBZn,but also to make reference for the design of the manufacture technique of preparations.[Methods]HBZn was synthesized by baicalin and zinc acetate in water with the pH value of 6.5～7.0.A further verification of the structure of HBZn was made by element analysis and the four spectra(IR,UV,MR,NMR ) analysis. High-performance liquid chromatography(HPLC ),atomic absorption spectrophotometry(AAS ),and EDTA coordination chemistry titration were used for determining the contents of HBZn,and the most appropriate method was validated.A preliminary quality control was established for HBZn about its characterization, identification,impurity test and assaying.According to the Pharmacopoeia of Chinese (2005 ) and other literatures reported,we investigated the product's stability including the influencing factors test,accelerated test and long-term stability test.[Results]The synthesis of HBZn,with water as a solvent had high yield and stable performance.The results of element analysis and four spectral contrast analysis showed that zinc ions should be combined with the carboxyl carbon of glucuronic acid of baicalin,and formed a big coordination bond with the root of acetate together, which was in line with the structure of HBZn we inferred before.By HPLC,it was found that the retention times of baicalin and HBZn were very near,that was to say, under the existing conditions,it would be difficult to separate HBZn from baicalin completely.Using AAS for the assay of HBZn,the results were in larger deviation from the theoretical values.Ashing the samples before the chemical titration method of EDTA was used to test the content of HBZn,and the determination accuracy(the recovery rate as high as 99.53%),precision(RSD = 0.323%),and linearity(linear equation:y = 0.6674x -0.1482,r = 0.9999 ) were good,and the results were reliable. HBZn was brick red powder with pungent odor,and almost insoluble in common organic solvents,its crystal water was volatile by heating.Aqueous solution of HBZn was in the pH value between 5.5～6.5,ignited residue content was less than 26%, heavy metals content was no more than 10 ppm,and arsenic salt content was no more than 2 ppm.The results of identification experiment indicated that HBZn was a coordination compound formed by baicalin complex with zinc ions,and the samples of synthesis were the products of HBZn expected.Temperature,humidity and light had a certain effect on the stability of HBZn,in particular,the content of HBZn declined evidently with the extension of time(P < 0.01 ).The results of accelerated testing and long-term stability test demonstrated that HBZn was basically stable under normal conditions,but there was a certain degree of degradation as time went by (content changed significantly,P < 0.01 ).[Conclusions]Zinc ions are combined with the carboxyl carbon of glucuronic acid of baicalin,and forms the coordination compound,HBZn.HBZn is brick red powder with pungent odor and poor solubility,its molecular formula is " Zn(C₂₁H₁₇O₁₁)(CH₃COO)·3.5H₂O ",and its molecular weight is 632.At present, EDTA titration method is used for the assay of HBZn.Through the review of the characters,identification,examination and assay of HBZn,a preliminary quality control can be made.HBZn is basically stable under normal conditions,the period of validity is set for two years temporarily,and we suggest that HBZn should be stored in cool,dry and dark environment.