国产盐酸多西环素原料中有关物质的结构鉴定及杂质谱考察  

Characterization of Related Substances and Study of Impurity Profile in Domestic Doxycycline Hyclate

作　　者：袁耀佐[1] 张玫[1] 钱文[1] 杨志明 赵恂[1] 

机构地区：[1]江苏省食品药品检验所,南京210008 [2]常州制药厂有限公司,常州213018

出　　处：《中国药品标准》2011年第2期106-111,共6页Drug Standards of China

摘　　要：目的:鉴定盐酸多西环素原料中检出的有关物质结构,考察国产原料的杂质谱。方法:用十八烷基硅烷键合硅胶为填充剂(pH值适用范围应大于9);以醋酸盐缓冲液[0.25 mol.L-1醋酸铵-0.1 mol.L-1乙二胺四醋酸二钠-三乙胺(100∶10∶1),用冰醋酸或氨水调节pH值至8.8]-乙腈(85∶15)为流动相;柱温35℃;检测波长为280 nm,流速:1.0 mL.min-1;进样体积:20μL。用土霉素、美他环素、β-多西环素对照品色谱保留时间定位方法鉴定3个已知杂质,用文献方法分别制备了4-表多西环素和4-表-6-表多西环素,再采用色谱保留时间定位方法鉴定其他2个杂质,用制备薄层色谱制备2-乙酰-2-脱碳酰胺多西环素溶液(采用LC-ESI-IT-MS2法鉴定其结构)鉴定另外1个主要杂质。结果:典型样品色谱图中检出8个杂质峰,6个主要杂质按色谱出峰顺序分别为土霉素、4-表-6-表多西环素、4-表-多西环素、美他环素、β-多西环素、2-乙酰-2-脱碳酰胺多西环素;杂质谱考察结果显示,不同来源的国产盐酸多西环素的杂质谱相似,均检出美他环素、β-多西环素、2-乙酰-2-脱碳酰胺多西环素及另外两未知杂质,但大多未检出土霉素。结论:建立的方法适用于盐酸多西环素原料中杂质谱考察和有关物质检查。Objectives： To identify the chemical structures of related substances in bulk of Doxycycline Hyclate and to study the impurity profile of Doxycycline Hyclate. Methods： Carry out the method with high performance liquid chromatogram, using a column packed with octadecysilane bonded silica gel and a mixture of a buffer solution which consist of 100 volumes of 0. 25 mol ·L-1 ammonium acetate solution, 10 volumes of 0. 1 mol ·L-1 ethyldiaminetetraaeetie acid disodium salt solution and 1 volume of triethyamine adjusting pH to 8.8 with glacial acetic acid acetonitrile （85：15 ） as the mobile phase, maintain the column temperature at 35℃, detection wavelength is 280nm, flow rate is l mL · min-1 , injection volume is 20 μL. Use oxytetracycline, metacyeline and β-epidoxycycline reference substances to identify and locate three impurities peaks in the chromatogram of a typical bulk of doxycycline hyclate, other two impurities were identified and located in the chromatogram by impurity solutions prepared according to literature methods, another impurity was located by a impurity solution which prepared by a preparative TLC method, and identified by LC-ESI-IT-MS：. Results： There are eight impurity peaks in a chromatogram of typical bulk of doxycycline hyclate, the six major impurity peaks are oxytetracycline, 4- epi-6-epidoxycline, 4- epidoxycline, metacycline, β-epidoxycycline and 2-acetyl-2-decarbamoyldoxycline respectively according to the elution order. The study showed that impurity profiles of different domestic doxycycline hyclate were similar, all include metacycline, β-epidoxycycline, 2-acetyl-2-decarbamoyldoxycline and other unknown impurities, but no oxytetracycline was detected from most doxycycline hyclate samples. Conclusions ： The established method was suitable to be applied in the study of impurity profile and test of related substances of doxycycline hyclate

关 键 词：盐酸多西环素 杂质谱 结构鉴定 

分 类 号：R927[医药卫生—药学]