Development and validation of an HPLC-UV method for the separation of entecavir optical isomers  

高效液相色谱法分离测定恩替卡韦光学异构体（英文）

作　　者：Dan Huang Daolin Zhang Nana Wang Xinhui Jiang 黄丹;张道林;王娜娜;蒋心惠(重庆医科大学药学院,重庆400016;重庆医药工业研究院有限责任公司,重庆400061;河南省漯河市第三人民医院,河南漯河462000)

机构地区：[1]School of pharmacy, Chongqing Medical University, Yuzhong District, Chongqing 400016, China [2]Chongqing Pharmaceutical Research Institute Co., Chongqing Engineering Research Center for Chemical Pharmaceutical Nan＇an District, Chongqing 400016, China [3]Luohe Third People＇s Hospital of Henan Province, Luohe, Henan 462000, China

出　　处：《Journal of Chinese Pharmaceutical Sciences》2018年第3期201-208,共8页中国药学（英文版）

基　　金：supported by Chongqing Pharmaceutical Research Institute and Pharmacy School of Chongqing Medical University partly

摘　　要：A simple and effective high-performance liquid chromatography with ultraviolet detection（HPLC-UV） method was established to determine entecavir optical isomers. With 3 chiral carbon atoms, entecavir had 7 optical isomers, including 6 diastereoisomers and 1 enantiomer. The separations were performed on a Symmetrix ODS-AQ C_（18） column（4.6 mm×250 mm, 5 μm） and a Daicel CHIRALPAK AD column（4.6 mm×250 mm, 10 μm）, respectively. The detection wavelength was set at 254 nm. The limit of detection（LOD） and the limit of quantification（LOQ） of diastereoisomers（diastereoisomer-1, diastereoisomer-2, diastereoisomer-3） were 0.0371, 0.0376, 0.0377, and 0.124, 0.125, 0.126 μg/mL, respectively. The LOD and LOQ of enantiomer were 0.14 and 0.46 μg/mL, respectively. The precision was within 0.36%, 0.44%, 1.04%, and 0.67% for diastereoisomer-1, diastereoisomer-2, diastereoisomer-3, and enantiomer, respectively. The recoveries of enantiomers ranged from 98.4% to 100.5%. The method could be applied to control the quality of entecavir.本文建立了一种简单有效的高效液相-紫外检测法测定分离恩替卡韦光学异构体。恩替卡韦化学结构中有3个手性原子,恩替卡韦有7个光学异构体,其中有6个非对映异构体,1个对映异构体。在Symmetrix ODS-AQ C_(18)(4.6 mm×250 mm,5μm)色谱柱上实现了恩替卡韦与非对映异构体的分离,在Daicel CHIRALPAK AD(4.6 mm×250 mm,10μm)色谱柱上实现了恩替卡韦和对映异构体的分离。检测波长为254 nm。非对映异构体(非对映异构体-1,非对映异构体-2,非对映异构体-3)的检测限和定量限分别为0.0371,0.0376,0.0377μg/mL和0.124,0.125,0.126μg/mL。对映体的检测限和定量限分别为0.14和0.46μg/mL。非对映异构体-1,非对映异构体-2,非对映异构体-3和对映异构体的精密度分别为0.36%,0.44%,1.04%和0.67%。对映异构体的回收率为98.4%–100.5%。该方法可用于控制恩替卡韦光学异构体的杂质限度。

关 键 词：ENTECAVIR Chiral separation DIASTEREOISOMERS ENANTIOMER HPLC-UV 

分 类 号：R917[医药卫生—药物分析学]