LC-MS/MS法分析萘普生钠中强制破坏后的降解产物

目的：采用色谱-质谱联用技术对萘普生钠中强制破坏后的降解产物进行结构鉴定。方法：采用CAPCELL PAK C₁₈色谱柱（250 mm×4.6 mm，5μm），以乙腈-水-甲酸（48：52：0.1）为流动相，检测波长为262 nm，流速为1.0 mL·min^-1，柱温35℃，进样量20μL，对萘普生钠的降解产物进行分离。同时，采用HPLC-QTOF MS对萘普生钠的主要降解产物进行定性研究。结果：在该色谱条件下，各降解产物峰和萘普生钠峰达到有效分离，并初步鉴定出萘普生钠中4个主要降解产物的结构。结论：本法可用于测定萘普生钠的降解产物，并对其药品质量控制提供了参考依据。

Objective: To identify the degradation compounds in naproxen sodium by liquid chromatographytandem mass spectrometry(LC-MS/MS). Methods: The sample was separated on a CAPCELL PAK C₁₈ column (250 mm×4. 6 mm, 5 μm)with the mobile phase consisting of acetonitrile-water-formic acid(48:52:0. 1) at a flow rate of 1. 0 mL·min^-1. The detection wavelength was set at 262 nm. The column temperature was 35℃ and the injection volume was 20 μL. The molecular structures of the degradation compounds of naproxen sodium were identified by HPLC-QTOF MS, and the main degradation compounds were identified in positive ion mode. Results: The degradation compounds were completely separated from naproxen sodium. Four major degradation compounds in naproxen sodium were preliminarily identified. Conclusion: The established method is useful for the determination and identification of the degradation compounds in naproxen sodium, which can be used in the quality control of naproxen sodium.

[1] 王丽君,王东凯,黎玲,等. HPLC法测定注射用萘普生钠的含量及有关物质[J].中国药剂学杂志, 2006, 4(1):16 WANG LJ, WANG DK, LI L, et al. Determination of naproxen sodium for injection with HPLC[J]. Chin J Pharm,2006,4(1):16
[2] 王国祥,宋宏春,宋士强,等.萘普生钠注射液的稳定性研究[J].中国药学杂志, 1992, 27(11):663 WANG GX, SONG HC, SONG SQ, et al. Study on the stability of naproxen sodium injection[J]. Chin Pharm J,1992, 27(11):663
[3] 中国药典2015年版.二部[S]. 2015:1211 ChP 2015. Vol Ⅱ[S]. 2015:1211
[4] EP 8. 0[S]. 2013:2830
[5] 杨俊玲,康新立. HPLC法测定萘普生钠片的含量[J].中国当代医药, 2011, 18(20):39 YANG JL, KANG XL. Determination of daidzein naproxen sodium tablets by HPLC[J]. China Mod Med,2011, 18(20):39
[6] 高磊,石嫱. HPLC法测定萘普生有关物质[J].中国药品标准, 2005, 6(6):17 GAO L, SHI Q. Examination of related substances in naproxen by HPLC[J]. Drug Stand China,2005, 6(6):17
[7] 刘玉春,许世辉. HPLC法测定萘普生钠注射液的含量[J].海峡药学, 2008, 20(11):60 LIU YC, XU SH. Determination of naproxen sodium injection by HPLC[J]. Strait Pharm J,2008, 20(11):60.
[8] 王国祥,宋宏春,宋士强,等.紫外分光光度法测定萘普生钠含量[J].内蒙古医学院学报, 1990, 12(1):35 WANG GX,SONG HC, SONG SQ, et al. Assay of naproxen sodium by ultraviolet spectrophotometry[J]. Acta Acad Med Nei Mongol, 1990, 12(1):35
[9] 陈寅生,马莉. HPLC法测定复方奈福泮萘普生钠缓释胶囊中两组分的含量[J].河南大学学报(医学版), 2011, 30(3):159 CHEN YS, MA L. Determination of the contents of two components in compound nefopam and naproxen sodium sustained release capsules by HPLC[J]. J Henan Univ(Med Sci), 2011, 30(3):159
[10] 沈炳香,李德刚,聂松柳. HPLC法同时测定萘普生钠伪麻黄碱缓释片中两组分的含量[J].安徽医药, 2007, 11(11):1002 SHEN BX,LI DG,NIE SL. Simultaneous determination of naproxen sodium and pseudoephedrine hydrochloride sustained-release tablets by HPLC[J]. Anhui Med Pharm J, 2007, 11(11):1002
[11] 李发美.分析化学.第七版[M].北京:人民卫生出版社,2008:1 LI FM. Analytical Chemistry. 7th ed[M]. Beijing:People' s Medical Publishing House,2008:1
[12] 刘丽梅,张富江,于海龙.萘普生合成工艺的研究[J].黑龙江医药, 2000, 13(4):214 LIU LM,ZHANG FJ,YU HL. Study on the new syntheitc process of naproxen[J]. Med J Heilongjiang,2000, 13(4):214
[13] 杨芳.萘普生及其中间体的合成和工艺改进[D].南京:南京理工大学, 2004 YANG F. The Synthesis of Naproxen and Its Intermediates[D]. Nanjing:Nanjing University of Science and Technology,2004
[14] 袁学军,苏增权,康敏,等.萘普生的不对称合成工艺改进[J]. 中国医药工业杂志,1999, 30(10):433 YUAN XJ, SU ZQ, KANG M, et al. The improvement of asymmetrical synthesis of naproxen[J]. Chin J Pharm, 1999, 30(10):433
[15] 李民前.高效低毒新药萘普生钠[J].华西药学杂志,1991, 6(1):57 LI MQ. Naproxen:a new drug of high activity and low poison[J]. West China J Pharm Sci,1991, 6(1):57
[16] HADI MA, RAGHAVENDRA RAO NG, SRINIVASA RAO A. Pharmacokinetic parameters determination and in vitro-in vivo correlation of ileocolonic-targeted pH-responsive coated minitablets of naproxen[J]. Sci Pharm,2015, 83(4):645