Impurity Study And Quality Analysis Of Calcitonin Salmon And Its Preparations

Salmon calcitonin is a kind of hormon,which is composed of32amino acids andhas high activity. It is used as the first choice of the treatment of osteoporosis,especiallyused for bone fracture treatment. As early as March1991,Novartis salmon calcitoninreceived FDA approval in the United States,the trade name of which is Miacalcin,today,this drug is still widely used. However due to the early use of this drug,the study ofimpurity did not carry out,there are few reports about its related substances. The impurityprofiles of different manufacturers are different,whether impurities have acitivity ornot,whether vivo and vitro potency result can reach consistency,these proplems will beexplored and studied. There are two method for the determination of biological potencyof salmon calcitonin,in vitro and in vivo,vitro method is superior to the vivo method.Wefound the problem of glassware for sample adsorption in the analysis process for thesalmon calcitonin injection.According to the above,the researches are as follows:1The study of related substances of salmon calcitonin and injectionsRelated substances of salmon calcitonin raw materials were detected by LC-MStechnology,determine whether it was a known impurity,determine the structure of them.There are two main process impurities,one is isomers,the other is lack of an asparagine.We use LC-MS technology,preparation,disulfide bond fracture analysis method todetermine the structure of the two injection degradation impurities,one impurity ishydrolysis product,and the other is three-sulfur bond polypeptide. The calcitonin Cimpurity is a kind of degradation product and can reflect the injection stability,wedeveloped impurity reference sample for injection impurities positioning analysis.Thereis a specific impurities in the injection of a factory,we analysised the sources of it,wefounded that the substance of butyl rubber stopper leached into the injection. Theimpurities studies of salmon calcitonin is a start and provide ideas for impurities researchof other synthetic peptides.2Vitro and in vivo activity of salmon calcitonin and its degradationIntend to establish and improve this method,and verify it. Further analysis the twodegradation impurities biological activity,we proved the consistency of the results ofin-vitro and in-vivo activity by experiments.3Analyze the quality of domestic and imported injectionWe analyze the quality of domestic and imported injection and solve problems arisingin quality analysis,compare salmon calcitonin injections of domestic and foreign. Establishment the HPLC method to measure the content of injectable powder. Examinewhether injection vials with and without silylation would adsorbe samples to serve as aguide role for the future experiments.We analysis the impurities of calcitonin salmon and its activities,establish theimpurity profile. We develop the calcitonin C reference substance and use HPLC todetermiantion the content of powder injection. We explore ways and means,accumulateexperimental data and provide a idea for the in-depth domestic salmon calcitonininjections quality conformance evaluation. This issue has some reference and guidancefor impurities study of other synthetic peptide drugs.