摘要
目的:制备盐酸多西环素中国药典2015年版(Ch P 2015)标准检测的紧邻主峰后杂质,并鉴定其结构。方法:以盐酸多西环素成盐用母液为对象,采用室温条件下半制备液相色谱分离纯化杂质;色谱条件:采用Synergi C_(18)(50 mm×250 mm,10μm)色谱柱,以0.1%三氟乙酸水溶液(A)-0.1%三氟乙酸乙腈溶液(B)为流动相,线性梯度洗脱(A-B):0.0 min(85∶15)→40.0 min(60∶40)→40.5 min(85∶15)?50.0 min(85∶15),流速为80 m L·min^(-1);254 nm检测收集目标组分,旋转蒸发去除有机溶剂,冷冻干燥制得目标杂质;采用盐酸多西环素Ch P 2015标准中有关物质检查的高效液相色谱法确证制得物质为目标杂质并采用归一化方法测定其纯度;采用光谱综合分析等手段确证其结构。结果:制得目标杂质纯度为98.7%,结构确证为2-乙酰-2-脱氨甲酰多西环素(即EP 8.0中的盐酸多西环素杂质F),在有关物质测定用供试品溶液中添加该杂质后,多西环素后相邻峰面积显著增加。结论:盐酸多西环素Ch P 2015标准检测的紧邻主峰后杂质经制备色谱分离并成功鉴定,该结论被Ch P 2015采用。
Objective： To prepare and identify the doxycycline hyclate impurity eluted right after the main component described in ChP 2015. Methods：The target impurity was isolated from doxycycline hyclate mother solution by a semi-preparetive HPLC with a Synergi RP-C18 column （ 250 mm× 50 mm, 10 μm ） at room temperature and gradient elution using mixtures of 0. 1% TFA in water（ A ）as A and 0. 1% TFA in acetonitile （ B ）as the mobile phase at a flow rate of 80 mL· min^-1. The liner gradient program of（ A-B ）was employed and set as follows ： 0.0 min （ 85 ： 15 ） →40.0 min （ 60 ： 40 ） →40.5 min （ 85 ： 15 ） →50.0 min （ 85 ： 15 ）. The analytes were monitored at a wavelength of 254 nm. The organic solvent of the collected targent impurity solution was evaporated by rotary evaporation and then was frozen to dry. The identity of the prepared target impurity was determined by the HPLC method described in ChP 2015 for the determination of the related substances of doycycline hyclate and its purity was calculated by normalization method. The chemical structure of the target impurity was identified by organic spectroscopic methods. Results： The purity of the prepared target impurity was 98.7% and the chemical structure of this impurity was identified as 2-acetyl-2-decarbamoyl-doxycycline and was confirmed to be the impurity F of doxycyeline hyclate described in EP 8.0. Conclusion： The doxycycline hyclate impurity eluted right after the main component described in ChP 2015 was successfully prepared with a semipreparetive HPLC method and identified. This result has been adopted by ChP2015.
作者
杨帆
张娅
张锦琳
杨志明
殷学智
赵述强
袁耀佐
张玫
YANG Fan ZHANG Ya ZHANG Jin-lin YANG Zhi-ming YIN Xue-zhi ZHAO Shu-qiang YUAN Yao-zuo ZHANG Mei(Hospital of Nanjing University of Science and Technology, Nanjing 210094, China Jiangsu Institute for Food and Drug Control, Nanjing 210008, China Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China Changzhou Pharmaceutical Factory, Changzhou 213018, China China Medical City Public Services Platform, Taizhou 225300, China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2017年第4期695-701,共7页
Chinese Journal of Pharmaceutical Analysis
关键词
四环素类抗生素
多西环素
杂质F
乙酰-脱氨甲酰多西环素
杂质制备
结构确证
tetracycline antibiotics
doxycycline
impurity F
acetyl-decarbamoyldoxycycline
impurity preparation
structural identification
