药学学报, 2019, 54(11): 1958-1964
引用本文:
林洁虹, 汪泓, 邵泓, 陈钢, 林梅. 基于质谱技术的手性氨基酸分析以控制消旋肽杂质的研究进展[J]. 药学学报, 2019, 54(11): 1958-1964.
LIN Jie-hong, WANG Hong, SHAO Hong, CHEN Gang, LIN Mei. Advances in research on mass spectrometry based chiral amino acid analysis for quality control of racemic peptide impurities[J]. Acta Pharmaceutica Sinica, 2019, 54(11): 1958-1964.

基于质谱技术的手性氨基酸分析以控制消旋肽杂质的研究进展
林洁虹1,2, 汪泓2, 邵泓2, 陈钢2, 林梅2
1. 中国医药工业研究总院上海医药工业研究院, 上海 201203;
2. 上海市食品药品检验所, 上海 201203
摘要:
手性氨基酸分析是一种灵敏、高效、经济的消旋肽杂质控制方法,尤其适用于氨基酸组成复杂的合成多肽药物。通过结合质谱检测的手性氨基酸分析可以获得消旋肽中非预期存在的氨基酸对映体组成,质谱技术还可以准确定位肽段中发生异构化的氨基酸手性中心,为消旋肽杂质的筛选,以及进一步实现微量消旋肽杂质的快速鉴定及定量奠定坚实基础,在控制合成多肽药物质量和以化学合成为基础的多肽药物设计研发中有重要作用。本文总结了多肽药物的水解方法;并对基于质谱技术的手性氨基酸分析的最新方法作简要综述,最后对合成多肽药物中消旋肽杂质的研究及控制方向进行了展望。
关键词:    合成多肽药物      消旋肽杂质      多肽水解      手性氨基酸分析      质谱     
Advances in research on mass spectrometry based chiral amino acid analysis for quality control of racemic peptide impurities
LIN Jie-hong1,2, WANG Hong2, SHAO Hong2, CHEN Gang2, LIN Mei2
1. Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai 201203, China;
2. Shanghai Institute for Food and Drug Control, Shanghai 201203, China
Abstract:
Chiral amino acid analysis is a sensitive, efficient and economical method for controlling racemic peptide impurities, especially for synthetic polypeptide drugs with complex composition of amino acids. Unexpected amino acid enantiomers in racemic peptides can be measured by chiral amino acid analysis coupled with mass spectrometry. The position of amino acid isomerization in the peptide segment can be accurately mapped by mass spectrometry, which lays a solid foundation for screening of racemic peptide impurities and rapid identification or quantification of trace racemic peptide impurities. Combination of the two techniques is vital for quality control of the synthetic polypeptide drugs and for research of polypeptide drugs based on chemical synthesis. The strategies of peptide hydrolysis have been summarized in this review. The latest chiral amino acid analysis based on mass spectrometry is briefly reviewed. Based on our knowledge, we have pointed to the direction of research and control of racemic peptide impurities in synthetic polypeptide drugs.
Key words:    synthetic polypeptide drug    racemic peptide impurity    peptides hydrolysis    chiral amino acids analysis    mass spectrometry   
收稿日期: 2019-04-28
DOI: 10.16438/j.0513-4870.2019-0335
基金项目: 国家自然科学青年基金资助项目(81803422).
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