Identification of the Related Substances in Etimicin Sulfate Detected Under the Condition of Chinese Pharmacopoeia 2010 by LC/MSn with Propionic Acid Enhanced Electrospray Ionization
YUAN Yao-zuo1, WU Yu-ning1,2, ZHAO Wei1, WANG Fang2, SU Xiao-chun3,TAN Li1, ZHANG Mei1* , HU Chang-qing4*
1.Jiangsu Institute for Food and Drug Control, Nanjing 210008, China; 2.China Pharmaceutical University, Nanjing 210009, China; 3. Changzhou Fangyuan Pharmaceutical Co. Ltd., Changzhou 213002, China; 4. National Institute for Control of Pharmaceutical and Biological Products, Beijing 100050, China
Abstract��OBJECTIVE To establish an LC/MSn method for identification of the related substances in etimicn sulfate detected under the chromatographic condition described in Chinese Pharmacopoeia 2010.METHODS The HPLC separation was carried out on a Welch Ultimate LP-C18 column(4.6 mm��300 mm,5 ��m)with mobile phase consisting of 0.2 mol��L-1trifluoroacetic acid(containing 0.1% propionic acid )-methanol(84��16) at a flow rate of 1.0 mL��min-1. Thirty percent of the eluent was detected by ion trap mass spectrometry, and the parent ions and the corresponding product spectra of all the related substances in etimicin sulfate were determined and elucidated.RESULTS Addition of 0.1% propionic acid into the mobile phase significantly enhanced the sensitivity of MS detector without altering the chromatographic behavior such as retention time and elution order of the related substances. Twenty-eight related substances were separated and detected by the LC/MSn method in a typical sample. Nine of them were identified with the help of corresponding impurity reference substances and 14 of them were elucidated by MS fragment information, while the other five were not identified due to limitated information. CONCLUSION The established method can be applied to the identification of the related substances in etimicn sulfate detected under the chromatographic condition described in Chinese Pharmacopoeia 2010, which is helpful to the quality improvement and process optimization of etmicin sulfate.
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YUAN Yao-zuo, WU Yu-ning, ZHAO Wei, WANG Fang, SU Xiao-chun,TAN Li, ZHANG Mei , HU Chang-qing. Identification of the Related Substances in Etimicin Sulfate Detected Under the Condition of Chinese Pharmacopoeia 2010 by LC/MSn with Propionic Acid Enhanced Electrospray Ionization. Chinese Pharmaceutical Journal, 2015, 50(20): 1790-1796.
XUE C X, ZHAO W J, LU Y F. Improved synthesis of etimicin sulfate[J]. Qilu Pharm Aff (��³ҩ��), 2005,24(2): 106-108.
[2]
DENG Y H. Clinical application and evaluation of safety of etimicin sulfate[J]. Chin J Clin Pharm(�й��ٴ�ҩѧ��־), 2005,13(5): 320-322.
[3]
The ICH SteeringCommittee. ICH harmonised tripartite guideline: impurities in drug substances [EB/OL]. 2006-10-25 [2009-10-08]. http://www. ich. org/LOB/m edia/MED IA422. Pdf.
[4]
LIU J, HU X L, SHEN Y Q, et al. Study on related products of etimicin[J]. Chin J Pharm(�й�ҽҩ��ҵ��־), 2000, 31(8): 358-360.
[5]
WANG H, ZHANG Z J, XIONG F,et al. Isolation and structure characterization of related impurities in etimicin sulfate by LC/ESI-MSn and NMR[J].J Pharm Biomed Anal,2011, 55 (5):902-907.
THOMAS M A. Ion suppress ion in mass spectrometry [J]. Clin Chem, 2003, 49(7):1041-1044.
[8]
YUAN Y Z, ZHANG M, QIAN W. Rapid characterization of the related substances in netilmicin sulfate sample by HPLC-ESI-IT-MSn[J].Chin Pharm J(�й�ҩѧ��־),2010,45(8):1428-1433.
[9]
YUAN Y Z, ZHANG M, FAN X L,et al.Impurity profiling of etimicin sulfate by liquid chromatography-ion trap mass spectrometry[J]. J Pharm Biomed Anal, 2012,70:212-223.
[10]
YUAN Y Z, ZHANG M, FAN X L,et al.Impurity profiling of micronomicin sulfate injection by liquid chromatography-ion trap mass spectrometry[J].J Pharm Biomed Anal, 2013,75: 94-104.
[11]
YUAN Y Z, ZHANG M, FAN X L,et al.Analysis vertilmicin by liquid chromatography-ion trap mass spectrometry [J]. J Pharm Biomed Anal, 2013,80:1-8.
[12]
ZHENG C N, HAO H P, WANG X, et al. Diagnostic fragmentation based extension strategy for rapid screening and identification of serial components of homologous families contained in traditional Chinese medicine prescript ion using high resolution LC-ESI-IT-TOF/MS: Shengmai injection as an example[J]. J Mass Spectrum, 2009,44(2): 230-244.
2015, Vol. 50 
