目的对注射用盐酸吉西他滨的主要杂质进行结构分析。方法采用液相色谱-四级杆飞行时间质谱联用技术对该杂质进行结构分析，色谱条件：采用ZORBAXEclipseXDB-C18(4.6mm×250mm，5μm)色谱柱，以甲醇-10mmol·L-1醋酸铵溶液（用醋酸调节pH至5.7）)（1∶9）为流动相，流速1.0mL·min-1；质谱条件：正离子检测模式，毛细管电压：4.0kV，锥孔电压：65V，喷雾气压：310kPa，干燥气（氮气）流量：11L·min-1，干燥气温度：350℃，碎裂电压150V；结吉西他滨与该杂质的多级质谱裂解规律，研究质谱碎片裂解途径，鉴定该杂质的结构。。结果该未知杂质为2′-脱氧-2′，2′-二氟尿苷。结论本实验为药物的杂质控制和工艺优化提供参数，进而提高用药安全性。
Abstract
OBJECTIVE To elucidate the structure of the major impurity in gemcitabine hydrochloride for injection.METHODS HPLC-QTOF-MS was adopted to analyze the structure of this impurity based on the fragmentation behavior of gemcitabine and this impurity. The separation was performed on a ZORBAX Eclipse XDB-C18(4.6 mm×250 mm, 5 μm) column. A mixture of 10% methanol and 90% 10 mmol·L-1 ammonium acetate（pH 5.7）was used as mobile phase. Flow rate was 1.0 mL·min-1. MS was performed under positive mode with 4.0 kV capillary voltage, 65 V skimmer, 310 kPa spray pressure, 11 L·min-1 drying gas (nitrogen) flow rate, 350 ℃ drying gas temperature and 150 V fragmentor.CONCLUSION This study offers scientific data for studying the origin of the impurity of gemcitabine hydrochloride and improving its quality.
关键词
注射用盐酸吉西他滨 /
杂质结构 /
高效液相色谱法 /
高分辨质谱
{{custom_keyword}} /
Key words
gemcitabine hydrochloride for injection /
impurity structure /
HPLC /
high resolution MS
{{custom_keyword}} /
中图分类号：
R917
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] JIN W,YANG Y J. Separation and determination of related substance in gemcitabine for injection by HPLC. Chin J Pharm Anal（药物分析杂志）,2004,24（5）;476-478. [2] HUANG M Z,WANG H R,CAI J,et al. Pharmacokinetics of gemcitabine in Chinese old patients with non-small cell lung cancer. Chin Pharm J（中国药学杂志）,2008,43(23);1819-1822. [3] USP34 . 2011;NF Monographs 2957. [4] WS1-（X-429）-2003Z（国家食品药品监督管理局国家药品标准新药转正标准）. 2004;139-141.[5] LI Y Z,LI C G,HU Y Z. Determination of gemcitabine hydrochloride and its related substances by HPLC . Haixia Pharm (海峡药学),2010, 22(６);67-70. [6] HONEYWELL R,LAAN A C,GROENINGEN C J,et al. The determination of gemcitabine and 2＇-deoxycytidine in human plasma and tissue by APCI tandem mass spectrometry. J Chromatogr B, 2007,847;142-152. [7] ZHENG Q M,LI X M,JIANG Y,et al. Establishment of LC-MS/MS method for determination of lamivudine. Chin J Pharm Anal（药物分析杂志）,2005,25(1);73-75. [8] YAN X,BRUCE K,GREM L. Measurement of the anticancer agent gemcitabine and its deaminated metabolite at low concentrations in human plasma by liquid chromatography-mass spectrometry. J Chromatogr B,2004,802;263-270. [9] WANG Y H,WANG X H,CHOU C B. The synthesis of gemcitabine hydrochloride. Chin J Pharm（中国医药工业杂志）,2007,38(4);249-251. [10]CAI D,SHANG L L,JIA Y H. Research development of cytosine. Chem Inter（化工中间体),2009,3(2);14-17
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
