Study On The Quality Control For 6-Fluoro-3-Chloromethylenethiochroman-4-One

As high lipid soluble full-sulphur atom heterocyclic compounds, thiochromanones have broad biological activities. They have attracted a widespread attention these years. 6-fluoro-3-(chloromethylene)-thiochroman-4-one(CMFT) is a novel compound with a new structure and independently designed and synthesized by our group. Related research showed that CMFT has certain anti-tumor biological activities. It has a broad development prospect and worth in-depth study.To ensure the quality of drugs, it is necessary to set up simple and effective quality standards with high specificity. In this dissertation, the physical and chemical properties of CMFT were studied in details. The results laid a firm foundation for the establishment of a reasonable and effective quality standard of CMFT.This dissertation consists of seven chapters.In chapter 1, the progresses in antineoplastic drugs and thiochromanones research were reviewed.In chapter 2, self contrast method and peak area normalization method in HPLC were established to determine the related substances of CMFT, respectively. The results showed that both of the two methods were simple, accurate and reliable. They could be applied for the analysis of the related substances of CMFT.In chapter 3, external standard method in HPLC and volumetric analysis method were used to determine CMFT. The HPLC results showed that good linearity for CMFT could be obtained in a range of 0.001 ~ 0.1 mg·mL-1(r = 0.9999). The average recovery was 99.2%, with corresponding RSD of 1.2%(n = 9) and good precision. The average recovery of volumetric analysis was 99.5%, with corresponding RSD of 0.3%(n = 9) and good precision. Compared the two methods, HPLC method was more simple. It could be applied for the determination of CMFT.In chapter 4, four residual solvents(including ethy formate, dichlormethane, n-hexane, and ethyl acetate) of CMFT were determined by capillary GC. The detected solvents were well separated and the blank test showed no interference. Good linearities obtained(r = 0.9990 ~ 0.9994) in the tested concentration ranges. The average recoveries were in the range of 100.5% ~ 118.2%. This method was simple, reliable and accurate for the detection of four residual solvents in CMFT.In chapter 5, CMFT quality standards(draft) on character, identification, test and assay were made, and drafting instructions were also presented.In chapter 6, the standardization of the purified CMFT(reference substance) was studied. HPLC was applied to determine the purity of reference substance. The results of normalization method and self contrast method showed that the purity was over 99.5 %. The stability of CMFT against high temperature, high humidity, and light was also studied. The results showed that CMFT should be preserved under seal in dark, cool and dry conditions.In chapter 7, conclusions were made.