Study On The Quality Of LAS API And FAA Tablets

LAS is tyrosine kinase inhibitors(TKI)。 It can cut the tumor cell survival and proliferation signals, but also can promote cell apoptosis, according to gene, cell receptor and regulatory molecules as drug attack target. So it has high curative effects, less toxic side effect. On the international, this kind of medicine has become a hot research of antitumor drugs.In this paper, according to the Chinese Pharmacopoeia (CH.P) and National drug application requirements, we studied the quality standards for 1.1 new drug LAS API and FAA tablets. In addition, we also studied the stability of LAS API.We established the HPLC method for determining the content of new drug LAS, by investigating the chromatographic column, mobile phase and detection wavelength, sample volume, velocity, etc. Experiments show that the detection limit was lng, the quantitation limit was 4ng, and the assay was validated in the concentration range of 10μg/ml～40μg/ml(r=0.9999,n=7). In addition, precision, repeatability is good (RSD<2%). The method can be used for the determination of the content of LAS.Established analysis method of related substances by LAS:The related substances were established by the HPLC and the preliminary structure of related materials was confirmed by HPLC-MS. The related substances Ⅱ was one of the LAS’s intermediates A4(5-(2-toluidine sulfonyl)-2-indolone). We speculated that it was LAS cis-trans isomerism, due to the related substances Ⅲ consistent with the level of mass spectrum of LAS.The method durability study was investigated by acid, alkali and oxidation test. The test showed that:the LAS was not stable in solution state. Degradation products were inspected. Besides, the degradation products and main peak were well-separated (R>1.5).A method was established for determination of residual organic solvents by headspace capillary GC. We looked at the heating temperature and heating time on the influence of residual solvent peak area. At the same time, we adopted temperature programmed to make each residue solvent’s peak shape is good, degree of separation greater than 1.5.We did inorganic check of LAS. The results showed that weightlessness, sulfate, ignition residue, heavy metal and arsenic salt were less than 0.5%,0.1%,0.1%,20ppm and 2ppm. We identified LAS by the way of chemical method, base and spectral chromatography. Furthermore, we described the LAS appearance, solubility, hygroscopicity, ultraviolet absorption and other physicochemical properties.Stability studies:we did the factors influencing test of LAS. Factors influencing test included high temperature, high humidity and strong light test. In addition, we did accelerated test(40℃±2℃, RH75%±5%) and long-term test(25℃±2℃, RH60%± 10%) of LAS. The results showed that LAS solid powder was stable. At the same time, long-term test was still ongoing.We did study quality standard and stability of FAA tablets. It included identification, the determination of dissolution rate, content and related substances etc. It provided the basis for the FAA tablet’s quality standard.The structure of LAS was new. Therefore the quality standard was obviously innovative and had important practical application.