高效液相色谱法分离测定恩替卡韦光学异构体

doi:10.5246/jcps.2018.03.021

中国药学(英文版) ›› 2018, Vol. 27 ›› Issue (3): 201-208.DOI: 10.5246/jcps.2018.03.021

高效液相色谱法分离测定恩替卡韦光学异构体

黄丹¹, 张道林², 王娜娜³, 蒋心惠^1*

1. 重庆医科大学药学院, 重庆 400016
2. 重庆医药工业研究院有限责任公司, 重庆 400061
3. 河南省漯河市第三人民医院, 河南漯河 462000

收稿日期:2017-12-13 修回日期:2018-01-10 出版日期:2018-03-31 发布日期:2018-02-26
通讯作者: Tel./Fax: +86-023-68485161, E-mail: jiangxinhui@cqmu.edu.cn

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

Dan Huang¹, Daolin Zhang², Nana Wang³, Xinhui Jiang^1*

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

Received:2017-12-13 Revised:2018-01-10 Online:2018-03-31 Published:2018-02-26
Contact: Tel./Fax: +86-023-68485161, E-mail: jiangxinhui@cqmu.edu.cn

摘要/Abstract

摘要：

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 C₁₈ (4.6 mm×250 mm, 5 µm) 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, 10 µm)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, 0.0377 µg/mL和0.124, 0.125, 0.126 µg/mL。对映体的检测限和定量限分别为0.14和0.46 µg/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: 恩替卡韦, 手性分离, 非对映异构体, 对映异构体, HPLC-UV

Abstract:

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 C₁₈ 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.

Key words: Entecavir, Chiral separation, Diastereoisomers, Enantiomer, HPLC-UV

中图分类号:

R917

Supporting:

黄丹, 张道林, 王娜娜, 蒋心惠. 高效液相色谱法分离测定恩替卡韦光学异构体[J]. 中国药学(英文版), 2018, 27(3): 201-208.

Dan Huang, Daolin Zhang, Nana Wang, Xinhui Jiang. Development and validation of an HPLC-UV method for the separation of entecavir optical isomers[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(3): 201-208.

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高效液相色谱法分离测定恩替卡韦光学异构体

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

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