Structure Identification and Quality Analysis of Relative Impurities of Recombinant Insulin Glargine
LI Jing1，LIANG Cheng-gang1，ZHANG Hui1，YANG Hua-xin1*，WANG Da-mei2
Author information+
1.National Institute for the Control of Pharmaceutical and Biological Products，Beijing 100050，China； 2.Gan Lee Pharmaceutical Co., Ltd.，Beijing 101102，China
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History+
Received
Published
2008-02-13
2008-10-10
Issue Date
2008-10-10
Abstract
OBJECTIVE To improve the quality of insulin glargine by identifying primary impurities and their source.METHODS Firstly,the purified impurities were spiked in the standard of insulin glargine and were determined by HPLC.Secondly,major impurities were indentified by HPLC peptide map.Molecular weight and peptide mass fingerprinting with obtained by MALDI-TOF,and validated by tricine SDS-PAGE,N-terminal sequencing and mass/mass spectrometry.RESULTS Major impurities were analogs of insulin glargine and relative to the enzymatic steps in the manufacture process.CONCLUSION This method is rapid,economical and accurate for identifying primary impurities of insulin glargine.The novel idea in analyzing the source of impurities can be a reference for the study of impurities in other insulin analogs.
LI Jing;LING Cheng-gng;ZHNG Hui;YNG Hu-xin;WNG D-mei.
Structure Identification and Quality Analysis of Relative Impurities of Recombinant Insulin Glargine [J]. Chinese Pharmaceutical Journal, 2008, 43(20): 1588-1592
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References
[1] ZOLTAN V，JANET F，WILLIAM C D. Recobinant DNA technology in the treatment of diabetes：insulin analogs[J] . Endocr Rev，2001，22 (5)：706-717.
[2] COPPOLINO R，COPPOLINO S，VILLARI V. Study of the aggregation of insulin glargine by light scattering[J] . J Pharm Sci，2006，95 (5)：1029-1034.
[3] HEINEMANN L，LINKESCHOVA R，RAVE K， et al. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo[J] . Diabetes Care，2000，23 (5)：644-649.
[4] PAYAM M，ABDOLHOSSEIN R N，HOSNIEH T. A rapid and sensitive method for simultaneous determination of insulin and A21-desamido insulin by high-performance liquid chromatography[J] . J Pharm Biomed Anal，2003，33 (1)：45-51.
[5] BRANGE J，LANGKJAER L，HAVELUND S， et al. Chemical stability of insuli. 1. Hydrolytic degradation during storage of pharmaceutical preparations[J] . Pharm Res，1992，9 (6)：715-726.
[6] Ch. P(2005) Vol Ⅱ(中国药典2005年版，二部)[S] . 2005：Appendix 33.
[7] ZHOU Y，OTTENS M，HANSEN E， et al. Human insulin and desamico human insulin isotherms in ethanol-water reversed phase systems[J] . J Chromatogr A，2004，1061 (2)：141-148.
[8] FRANK B H，CHANCE R E. Therapeutic agents produced by genetic engineering[C] . 1st ed. Symposium，Group：Toulouse-Labege：Sanofi Group，1985：138-142.
[9] CHANCE R，GLAZER N，WISHNER K. Biopharmaceuticals[M] . 1st Dordrednt：Kluwer Academic Publishers，1999：149-151.
[10] JARS M U，HVASS A，WAABEN D. Insulin aspart (AspB28 human insulin) derivatives formed in pharmaceutical solutions[J] . Pharm Res，2002，19 (5)：621-628.
[11] THOMAS A，THEVIS M，DELAHAUT P， et al. Mass spectrometric identification of degradation products of insulin and its long-acting analogues in human urine for doping control purposes[J] . Anal Chem，2007，79 (6)：2518-2524.
[12] SENSTIUS J，HARBOE E，WESTERMANN H. In vitro stability of insulin aspart in simulated continuous subcutaneous insulin infusion using a minimed 508 insulin pump[J] . Diabetes Technol Ther，2007，9 (1)：75-79.
