核磁共振和液相色谱-质谱法对苯丙哌林未知杂质的结构分析  

Structural analysis of unknown impurities in benproperine by NMR spectroscopy and liquid chromatography-mass spectrometry

作　　者：孙煌 付璀莹 周润宏 白政忠 

机构地区：[1]黑龙江省食品药品检验检测所,哈尔滨150088

出　　处：《药物分析杂志》2017年第11期2000-2005,共6页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立利用仪器分析苯丙哌林未知杂质化学结构的方法,并对2个未知杂质进行结构确证。方法:采用Inertsil ODS-3(4.6μm,2.1 mm×150 mm)色谱柱,以甲醇-0.01 mol·L^(-1)醋酸铵缓冲液(取醋酸铵0.77 g,加水800 m L溶解,用冰醋酸调节p H至3.3,用水稀释至1 000 m L)(65∶35)为流动相,流速0.25 m L·min^(-1),检测波长270 nm。用HPLC-MS/MS分析2个未知杂质,使用制备液相进行分离纯化,通过核磁共振(~1H-NMR、^(13)C-NMR、HMBC、HSQC、DEPT135、H-H COSY)技术,对苯丙哌林及其未知杂质进行结构确证。结果:首次发现并确定苯丙哌林2个未知杂质的结构,分别为1-[2-(2-苯甲酰基苯氧基)-1-甲基乙基]哌啶和1-[2-(2-苄基-6-氯苯氧基)-1-甲基乙基]哌啶。结论:该方法可为苯丙哌林的质量控制提供依据。Objective： To establish a method for the determination of unknown impurities in benproperine and identify the structure of two unknown impurities, Methods： An Inertsil ODS-3 （ 4.6 μm, 2.1 mm × 150 mm） column was adopted for the study. The mobile phase was methanol - 0.01 mol· L-1sodium acetate buffer solution （ Take ammonium acetate 0.77 g, dissolved by 800 mL of water, adjust the pH to 3.3 by acetic acid, diluted with water to 1 000 mL ） （ 65 ： 35 ）. The flow rate was 0.25 mL·min-1, the detection wavelength was 270 nm. Two impurities were analyzed by HPLC-MS/MS, and was then separated and purified by preparative HPLC, and the structure were confirmed by nuclear magnetic resonance （ 1H-NMR, 13C-NMR, HMBC, HSQC, DEPT135, H-H COSY ）. Results： Two unknown impurities were 1-[ 2- （ 2-benzoylphenoxy ） -1-methylethyl ] piperidine and 1- [ 2-（ 2-benzyl-6-chlorophenoxy ）-1-methylethyl ] piperidine. Conclusion： The established method can provide a comprehensive reference for quality control of benproperine.

关 键 词：苯丙哌林 有关物质 核磁共振波谱 液相色谱质谱联用 波谱归属 杂质结构确证 

分 类 号：R917[医药卫生—药物分析学]