Study On The Quality Standard Of Two Kinds Of New Drugs

Study on the quality standard of drug is very important in drug research and development. Quality control includes not only studies on substance drug and preparation, but also on accessory, packing material and various keys such as the discovery, produce, store, transportation of new drug,in order to ensure safe, effective, and controlled for drug. The thesis mainly include a system research on quality standards of polymer drug (PGA-Ala-TXL) and chiral drug (R, R)-penenhuclidine fumarate.The first part gave a detailed study on quality standards of polymer drug (PGA-Ala-TXL),this part consisted of four chapters.The first chapter was to establish the reversed-phase high performance liquid chromatographic (RP-HPLC) methods for the purity control of the conjugates of poly- glumatic acid with paclitaxel (PGA-Ala-TXL) according to property of PGA-Ala-TXL.Two RP-HPLC methods were used to separate and quantify the conjugates and its related impurities such as free poly- glumatic acid and paclitaxel.The validations of the two methods were also investigated.In chapter two, the purity check and the quantitative analysis of the polymer drug substance and the related impurities, such as the free polyglutamic acid, the free paclitaxel, were accomplished by the two methods developed above. The stabilities of the drug were investigated under the conditions of room temperature, high temperature(60℃) , high temperature(40℃) , lighting(4500 lx), high humidity(RT 25℃RH 92.5%), high humidity(RT 25℃RH 75%), 4℃, freeze(-20℃) and so on, to offer evidence for the package, storage and transport of the drug.In chapter third, the molecular weight and the coupled site of the polymer drug were determined. The structure of the drug was further identified to ensure nature of itself. In order to evaluate the bounded amount of the active component which has significant influence on pharmaceutical therapy, the UV method was employed to measure the binding ratio of paclitaxel to PGA-Ala-TXL.The second part gave a detailed study on the quality standards of chiral drug (R, R)-penehyclidine fumarate. This part consisted of four chapters.In chapter first, RP-HPLC and chiral additive mobile phase HPLC of (R, R)-penehyclidine fumarate were developed. The method validation of the RP-HPLC was also investigated.In chapter second, RP-HPLC method, chiral additive mobile phase HPLC method and thin-layer chromatography method were used to check the purities of three batches of samples and reference. The amounts of the residual solvents were determined using gas chromatography. These results provided evidences for the quality control of the drug.In chapter third, the stabilities of the active pharmaceutical ingredients were investigated according to quality standard establishedunder the conditions: heating, humility, lighting and so on. These results also provided evidences for the package, storage and transport of the drug. The accelerated testing and the long-term testing were carried out to determine the period of validity.In chapter fouth, the solubility, the hygroscopicity, the optical rotation and the loss on drying were investigated to provide evidences for the establishing of the quality standard.