比阿培南及杂质质控HPLC分析方法的建立

doi:10.5246/jcps.2011.02.022

比阿培南及杂质质控HPLC分析方法的建立

王楠, 李春凤, 张斗胜, 胡昌勤^*

中国药品生物制品检定所, 北京 100050

收稿日期:2010-09-24 修回日期:2011-01-10 出版日期:2011-03-15 发布日期:2011-03-15
通讯作者: 胡昌勤*

Establishment of an HPLC method for the analysis of biapenem and its impurities

Nan Wang, Chun-Feng Li, Dou-Sheng Zhang, Chang-Qin Hu^*

National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100050, China

Received:2010-09-24 Revised:2011-01-10 Online:2011-03-15 Published:2011-03-15
Contact: Chang-Qin Hu*

摘要/Abstract

摘要：

建立了适用于比阿培南及其杂质质量控制的HPLC分析方法。采用Dikma Diamonsil C18(250 mm×4.6 mm, 5 mm) 色谱柱, 流动相为乙腈-0.1%三乙胺溶液 (1:99, v/v), 二极管阵列检测器检测波长为220 nm。比阿培南的线性范围为(0.05-10.0) mg/mL (r² = 0.999); 杂质的最低检出限 (LOD) 和最低定量限 (LOQ) 分别为4.8 ng (S/N = 3) 和 18.5 ng (S/N = 10); 测定比阿培南最大杂质和总杂质的日内精密度 (RSD) 分别为1.84% 和 3.37% (n = 3), 日间精密度 (RSD) 分别为4.84% 和 7.58% (n = 9); 供试品溶液在4 ºC放置6 h 稳定。利用HPLC-DAD数据, 采用二维色谱光谱相关分析技术, 在没有杂质对照品的情况下, 实现了质控分析HPLC-UV色谱图中的色谱峰与LC-MS色谱图中的色谱峰的相互识别。质控色谱图中相对保留时间为0.528, 0.743, 1.062和2.817的4个色谱峰结构被确认, 分别为比阿培南的水解产物和二聚体。该方法为鉴别常规HPLC-UV色谱图中的色谱峰提供了新思路。

关键词: 比阿培南, HPLC-DAD, 二维色谱光谱相关分析, 鉴别, 杂质

Abstract:

An HPLC method for routine quality control of biapenem was established. A Dikma Diamonsil C18 column (250 mm×4.6 mm, 5 µm) was used with diode array detection and single wavelength detection at 220 nm. The mobile phase was consisted of acetonitrile-0.1% triethylamine water (1:99, v/v). The liner range for biapenem quantification was 0.05-10.0 mg/mL (r²= 0.999). The LOD and LOQ of impurity were 4.8 ng (S/N = 3) and 18.5 ng (S/N = 10), respectively. Intra-day RSD of main impurity and total impurity were 1.84% and 3.37% (n = 3); inter-day RSD of main impurity and total impurity were 4.84% and 7.58% (n = 9). The test solution was stable when stored at 4 ºC for 6 h. The impurity peaks of biapenem can be identified by chromatographic spectral correlation analysis using high-performance liquid chromatography-diode array detection data from the quality control method by calculating correlation coefficients without reference standards. Two hydrolysis degradation products with relative retention times (RRTs) of 0.528 and 0.743, two dimers with RRTs of 1.062 and 2.817 were identified in the quality control chromatogram. It provides a new way to identify impurity peaks by the routine HPLC-UV method.

Key words: Biapenem, HPLC-DAD, Two-dimensional chromatographic spectral correlative map, Identification, Impurities

中图分类号:

R917

Supporting: Foundation item: National Key New Drug R&D Program Foundation of China (Grant No. 2009ZX09313-027).
^*Corresponding author. Tel.: 86-10-67095308; fax: 86-10-65115148

王楠, 李春凤, 张斗胜, 胡昌勤^*. 比阿培南及杂质质控HPLC分析方法的建立[J]. , DOI: 10.5246/jcps.2011.02.022.

Nan Wang, Chun-Feng Li, Dou-Sheng Zhang, Chang-Qin Hu^*. Establishment of an HPLC method for the analysis of biapenem and its impurities [J]. , DOI: 10.5246/jcps.2011.02.022.

参考文献

[1] Hu, C.Q. Sci. China Chem. 2010, 40, 679-687.
[2] Q3A (R2): Impurities in New Drug Substances, International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use, Geneva. 2006, http://www.ich.org
[3] European Pharmacopoeia. 7th ed. Council of Europe, Strasbourg. 2010, 559.
[4] The United States Pharmacopoeia. 33th ed. US Pharmacopeial Convention, Rockville, MD. 2010, 187.
[5] China Pharmacopoeia Commission. Pharmacopoeia of the People's Republic of China. Part. II, Beijing: China Medical Science and Technology Press, 2010, Appendix 205.
[6] Nageswara, R.R; Nagaraju, V. J. Pharm. Biomed. Anal. 2003, 33, 335-377.
[7] Kovaleski, J.; Kraut, B.; Mattiuz, A.; Giangiulio, M.; Brobst, G.; Cagno, W.; Kulkarni, P.; Rauch T. Adv. Drug Deliv. Rev. 2007, 59, 56-63.
[8] Li, J.; Zhang, D.S.; Yao, S.C.; Hu. C.Q. Sci. Sin. Chim. 2010, 40, 77-785.
[9] Xia, M.; Hang, T.J.; Zhang, F.; Li, X.M.; Xu, X.Y. J. Pharm. Biomed. Anal. 2009, 49, 937-944.
[10] Prasada, R.K.V.V.; Rani, A.; Raghava, R.A.V.; Bharathi, C.H.; Ramesh, D.; Naidu, A. J. Pharm. Biomed. Anal. 2007, 43, 1476-1482.
[11] Bharathi, C.H.; Prasad, C.S.; Vijaya, B.D. J. Pharm Biomed. Anal. 2007, 43, 733-740.
[12] Li, W.; Hu, C.Q. J. Chromatogr. A. 2008, 1190, 141-149.
[13] Li, W.; Hu, C.Q.; Jin, S.H. Acta Pharm Sin. 2007, 42, 1292-1297.
[14] Ikeda, K.; Ikawa, K.; Ikeda, A.; Nishikawa, Y.; Morikawa, N. J. Chromatogr. B. 2006, 844, 148-152.
[15] Moffat, A.C.; Trafford, A.D.; Jee, R.D.; Graham, P. Analyst. 2000, 125, 1341-1351.
[16] Jenke, D.R.; William, B.; Lake, R. J. Liq. Chromatogr. Relal. Technol. 1996, 19, 719-736.
[17] Analytical Methods Committee. Analyst. 1988, 113, 1469-1471.
[18] Sajonz, P.; Natishan, T.K.; Wu, Y.; Williams, J.M.; Pipik, B.; DiMichele, L.; Novak, T.; Pitzenberger, S.; Dubost, D.; Almarrson, ö. J. Liq. Chromatogr. Relal. Technol. 2001, 24, 2999-3015.