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.doc

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 孙煌付璀莹周润宏白政忠 黑龙江省食品药品检验检测所 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. 6 U m, 2. 1 mmX 150 mm）色谱柱, 以甲醇-0. 01 mol ? L醋酸鞍缓冲液（取醋酸鞍0. 77 g,加水800 m L溶解，用 冰醋酸调节pH至3. 3,用水稀释至1 000 n）L） （65 : 35）为流动相，流速0. 25 m L -min1,检测波长270 nmo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C1H-NMR、C-NMR、HMBC、HSQC、DEPT135、IH1 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] 哌旋和1-[2- （2-节基-6-氯苯氧基）-1-甲基乙基]哌旋。结论:该方法可为苯丙 哌林的质量控制提供依据。 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； 作者简介:孙煌 Tel:E-mai 1: limsn@163. com 收稿日期：2016年11月21日 Struetural analysis of unknown impurities in benproperine by NMR spectroscopy and liquid chromatography-mass spectrometry SUN Huang FU Cui-ying ZHOU Run-hong BAI Zheng-zhong Heilongjiang Institute for Food and Drug Control; Abstract： 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 u m, 2. 1 mmX 150 mm) column was adopted for the study.The mobi1e phase was methanol_0. 01 mol ? I/1 sodium acetate buffer solution (Take ammonium acctate 0. 77 g, dissolved by 800 m L of water, adjust the p H to 3. 3 by ace tic acid, dil uted with water to 1 000 m L) (65 : 35)? The flow rate was 0. 25 m L ? min the detection wave 1 eng th was 270 nm. Two impur ities were analyzed by I1PLC-MS/MS, and was then separated and purified by preparative HPLC, and the structure were confirmed by nuclear magnetic resonance (~1II-XMR, C-NMR, UMBC, IISQC, 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 qual ity control of benproperine. Keyword： benproperine; related substances; N\1R; HPLC-MS/MS; assignment; structure identification of impunity; Received： 2016 年 11 月 21 日 苯丙哌林（benproperine