| Summary: | 碩士 === 朝陽科技大學 === 應用化學系碩士班 === 91 === This research is focused on the study of Sesamol, which is the main chemical intermediate used in the manufacture of the antidepressant drug called Paroxetine. The main objectives of this study are: 1) The identification of Sesamol’s impurities, including their physical and chemical properties. That information would be helpful for the drug manufacturer to reduce the production cost. 2) Comparison of the impurities analysis results using two different analysis methods (Gas chromatography and High Performance Liquid Chromatography) and select the one which can be more suitable for the monitoring of the In-Process chemical reaction control. The source of the Sesamol sample was the industrial grade reagent made by Sinon company (Taiwan). The procedure of this research starts with the GC-MS analysis of the Sesamol sample. Based on the GC-MS analysis, the main ingredient, along with the four detectable impurities were shown on the mass spectra (I, II, III, IV). However, the mass spectra library failed to identify the two names (II, III) out of the four impurities. To find out the names of those two chemicals, we synthesized the impurity (II, III) and purified the Sinon company‘s sesamol for standard. Then, the remaining two impurities (I, IV) were bought from TCI Co. and other companies from PROC. To separate the impurities from each other, HPLC and PLC (Preparative Liquid Chromatography) were applied to find out the best separation condition for the impurities and collect them one by one (collected by PLC). Once the purified impurities were obtained, the exact chemical structures of each impurity were determined by using a combination of NMR, FTIR, GC-MS and HPLC. Finally, all the Sesamol’s impurities were analyzed using both GC and HPLC for analytical comparison.
The names of the four Sesamol derived impurities are: 1,3-Benzodioxole (C7H6O2), 1,3-Benzodioxole-formate ester (C8H6O4), Sesamol acetate (C9H8O4), 1,3-Benzodioxole-5-carboxaldehyde (C8H6O3). Based on the GC analysis results of Sesamol and It’s impurities, it was understood that the linearity constant ( r ) was good (over 0.980) and the LOD plus LOQ were 5~7×10-3ng (except for 1,3-Benzodioxole-formate ester which has LOD of 0.240ng) and 1.8~80.1×10-2ng respectively. On the other hand, the analysis results from HPLC were even better with ( r ) value over 0.999 plus the LOD and LOQ values of 6~23×10-2ng and 21~75×10-2ng respectively. Conclusion: Due to the low volatility of 1,3-Benzodioxole-formate ester, high polarity which, tends to remain in GC’s column plus its high CV% value, it would be more suitable to use HPLC as the tool for drug manufacturer’s monitoring of the In-Process chemical reaction control. Even though the GC can detect all four impurities in Sesamol, It would be more preferable to measure the Sesamol using HPLC.
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