本文關(guān)鍵詞：原料藥MF的質(zhì)量標(biāo)準(zhǔn)研究　出處：《河南大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： MF 喹諾酮類抗菌藥物 質(zhì)量標(biāo)準(zhǔn)研究 高效液相色譜法 氣相色譜法

【摘要】：喹諾酮類抗菌藥是一類合成抗菌藥,具有廣譜、半衰期長、不良反應(yīng)少等優(yōu)點(diǎn)。本課題采用多種分析技術(shù)對新藥MF進(jìn)行質(zhì)量標(biāo)準(zhǔn)研究,并對各項(xiàng)研究方法進(jìn)行完整地方法學(xué)驗(yàn)證,以此制定出MF的質(zhì)量標(biāo)準(zhǔn)草案。 首先,根據(jù)化學(xué)藥品結(jié)構(gòu)確證研究的指導(dǎo)原則,對合成的MF樣品進(jìn)行了化學(xué)結(jié)構(gòu)確證。包括元素分析、紫外吸收光譜(UV)、紅外吸收光譜(IR)、質(zhì)譜(MS)、核磁共振氫譜(1H-NMR)、核磁共振碳譜(13C-NMR)、氫-氫相關(guān)譜(H-H COSY)、碳-氫相關(guān)譜(HSQC,HMBC)、核磁共振DEPT試驗(yàn)、差熱分析等分析,證明合成的MF化學(xué)結(jié)構(gòu)與目標(biāo)化合物相符。 其次,本文對樣品進(jìn)行了有關(guān)物質(zhì)、含量的高效液相色譜(HPLC)的方法研究,分別對色譜柱、流動(dòng)相、流速和柱溫進(jìn)行考察,建立測定有關(guān)物質(zhì)、含量的最佳液相色譜條件：Agilent1260液相系統(tǒng)；色譜柱為Agilent ZORBAX Eclipse XDB-phenyl (4.6×250mm,5μm);流動(dòng)相為甲醇：水相(0.5mg/m1四丁基硫酸氫銨,1mg/ml磷酸二氫鉀,2m1磷酸調(diào)pH2)=28：72；檢測波長為293nm；柱溫為45℃；流速為1.3ml/min。經(jīng)定位和破壞性試驗(yàn)驗(yàn)證,證明本品與有關(guān)物質(zhì)中的雜質(zhì)分離良好,并對建立的方法進(jìn)行方法學(xué)驗(yàn)證。經(jīng)檢測,三批樣品的有關(guān)物質(zhì)含量均小于0.3%,含量測定的結(jié)果均為在98.0%-102.0%之間。 再次,本文建立了MF殘留溶劑檢查的氣相色譜方法。最佳的氣相色譜條件為：氣相色譜儀為Agilent Technologies6890N;頂空進(jìn)樣器為Agilent7694E;色譜柱為DB-wax (30.0m×0.53mm×1.00μm)毛細(xì)管柱；采用氫火焰離子化檢測器(FID),檢測器溫度：250℃；柱溫：40℃保持8min,以40℃/min的速率升至200℃,保持3min；載氣(高純氮?dú)?；恒壓：壓力4psi,頂空進(jìn)樣溫度80℃,平衡時(shí)間20min,進(jìn)樣量2m1。經(jīng)過方法學(xué)驗(yàn)證,表明該方法線性良好、靈敏度高,重現(xiàn)性良好。檢測三批樣品按外標(biāo)法以峰面積計(jì)算,甲醇和乙腈殘留量均小于標(biāo)準(zhǔn)限度0.3%、0.041%,其他溶劑未檢出。 最后,對該原料藥的理化特性和穩(wěn)定性進(jìn)行考察。影響因素試驗(yàn)表明,該原料藥對強(qiáng)光、高熱及高濕均較穩(wěn)定；采用效仿上市藥物的包裝通過加速6個(gè)月,長期12個(gè)月后,藥物在日常條件下穩(wěn)定,但在高濕環(huán)境下略有吸濕增重的現(xiàn)象,但含量、有關(guān)物質(zhì)等均無明顯變化,質(zhì)量較穩(wěn)定。 經(jīng)過上述一系列試驗(yàn),為MF原料藥制定出質(zhì)量標(biāo)準(zhǔn)草案提供了依據(jù),同時(shí)為制劑的研發(fā)和生產(chǎn)工藝的設(shè)計(jì)奠定了基礎(chǔ)。
[Abstract]:Quinolones are a class of synthetic antimicrobial agents, with the advantages of broad spectrum, long half-life, less adverse reactions, etc. In this paper, a variety of analytical techniques were used to study the quality standard of new drug MF. And complete methodology validation of the various research methods, so as to formulate the draft quality standards for MF. Firstly, according to the guiding principles of chemical structure identification, the chemical structure of the synthesized MF samples was confirmed, including elemental analysis, UV absorption spectra and IR absorption spectra. MS-MS, 1H-NMR-NMR, 13C-NMR-NMR, H-H COSYN, HSQC. The chemical structure of the synthesized MF was confirmed to be consistent with the target compound by HMBCX, NMR DEPT test and differential thermal analysis. Secondly, the related substances, the content of HPLC were studied, the chromatographic column, mobile phase, flow rate and column temperature were investigated, and the related substances were determined. The optimum liquid chromatographic conditions of the content were: 1: Agilent 1260 liquid phase system; The chromatographic column was Agilent ZORBAX Eclipse XDB-phenyl (4.6 脳 250mm) 5 渭 m. The mobile phase is methanol: water phase: 0.5 mg / m 1 tetra#china_person0# ammonium hydrogen sulfate 1 mg / ml potassium dihydrogen phosphate 2m1 phosphoric acid adjusts pH 2: 72; The detection wavelength was 293nm; The column temperature is 45 鈩，

本文編號：1421847