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期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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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(英文):
分类号:R917
出版年·卷·期(页码):2017,37 (11):2000-2005
DOI: 10.16155/j.0254-1793.2017.01.01
-----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 μm,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 mL溶解,用冰醋酸调节pH至3.3,用水稀释至1 000 mL)(65∶35)为流动相,流速0.25 mL·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、13C-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。

-----英文摘要:---------------------------------------------------------------------------------------

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-1 sodium 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.

-----参考文献:---------------------------------------------------------------------------------------
[1] Martindale:the Extra Pharmacopoeia 37th Edition[S].2016:1552
[2] 钱之玉.药理学[M].北京:中国医药科技出版社, 2009:478 QIAN ZY.Pharmacology[M].Beijing:China Medical Science Press, 2009:478
[3] 中国药典2015年版.二部[S].2015:1571 ChP 2015.Vol Ⅱ[S].2015:1571
[4] 刘克江,陈怡.HPLC法测定磷酸苯丙哌林颗粒的含量[J].天津药学, 2004,16(4):10 LIU KJ, CHEN Y.Determination of benproperine phosphate granules by HPLC[J].Tianjin Pharm, 2004,16(4):10
[5] 欧阳冬华, 朱丹利, 陈雅萍.HPLC法测定磷酸苯丙哌林片的含量[J].安徽医药,2008;12(2):135 OUYANG DH,ZHU DL,CHEN YP.Determination of benproperine phosphate tablets by HPLC[J].Anhui Med Pharm J, 2008,12(2):135
[6] 王蓓, 高慧钦.磷酸苯丙哌林口服溶液的有关物质研究[J].现代中西医结合杂志, 2007, 16(8):1085 WANG B, GAO HQ.Study of benproperine phosphate related substances by HPLC[J].Mod J Integr Tradit Chin Western Med, 2007, 16(8):1085
[7] 傅强,贺浪冲,郭琦,等.高效液相色谱法测定磷酸苯丙呱林含量及有关物质[J].药物分析杂志, 2006,26(1):55 FU Q, HE LC, GUO Q, et al, HPLC determination of benproperine phosphate and its related substances[J].Chin J Pharm Anal, 2006,26(1):55
[8] 张军武, 赵琦.磷酸苯丙哌林口服液中有关物质检查方法的改进[J].西北药学杂志, 2008,23(4):205 ZHAN JW,ZHAO Q.Improvement of detection of related substances in benproperine phosphate oral liquid[J].Northwest Pharm J, 2008,23(4):205
[9] 姚新生, 陈英杰, 徐绥绪,等.超导核磁共振波谱分析[M].北京:中国医药科技出版社, 1991:151 YAO XS, CHEN YJ, XU SX, et al.NMR Spectrometer with Superconducting Magnet[M].Beijing:China Medical Science Press, 1991:151
[10] LISE SCHJELDERUP, ARNE JORGEN AASEN.The absolute configuration of benproperinium dihydrogen phosphate, an antitussive drug[J].Chirality,1989,1(1):86
[11] LI Y, ZHONG DF, CHEN SW, et al.Identification of some benproperine metabolites in humans and investigation of their antitussive effect[J].Acta Pharmacol Sin,2005,26(12):1519
[12] 黄海华, 崔洪霞, 钟大放,等.利用微生物转化模型研究苯丙哌林的代谢产物[J].中国药理学与毒理学杂志, 2001,15(4):297 HUANG HH, CUI HX, ZHONG DF, et al.Study on metabolites of benproperine using microbial model of transformation[J].Chin J Pharmacol Toxicol, 2001,15(4):297
[13] 桂静, 宋林, 王凌.人血浆中磷酸苯丙哌林的测定及其缓释制剂在人体内的生物等效性研究[J].华西药学杂志, 2010,25(3):296 GUI J,SONG L,WANG L.Determination of Benproperine phosphate in human plasma and bioavailability study of its preparations in healthy volunteers[J], West China J Pharm Sci, 2010,25(3):296
[14] 孙煌, 娄志红, 付璀莹,等.核磁共振和液相色谱-质谱法对多索茶碱未知杂质的结构分析[J].药物分析杂志, 2013, 33(3):443 SUN H, LOU ZH, FU CY, et al.Structural analysis of an unknown impurity in doxofylline by NMR spectroscopy and liquid chromatography-mass spectrometry[J].Chin J Pharm Anal, 2013,33(3):443
[15] 董宇,王晓黎,曲建国.应用高效液相色谱-飞行时间质谱及离子阱质谱分析磷酸苯丙哌林中的杂质[J].中国药学杂志,2012,47(19):1585 DONG Y, WANG XL, QU JG.Analysis of impurity in benproperine phosphate bulk drug by high performance liquid chromatography-time of flight mass spectrometry and ion trap mass spectrometry[J].Chin Pharm J,2012,47(19):1585

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