摘要
目的建立基于高效液相色谱-四级杆飞行时间串联质谱(HPLC-Q/TOF-MS/MS)的棘白霉素B母核(ECBN)及其杂质的结构解析策略。方法通过HPLC-Q/TOF-MS/MS对ECBN的碎片离子进行解析,总结了①~④4条碎片离子裂解途径,这4条裂解途径包括特征性b、y离子及氨基酸残基离子。另外,由于ECBN中含有较多羟基(8个)导致产生连续脱水离子峰,可以辅助推断ECBN类似物的结构。结果本研究首次建立了系统、完善的ECBN的结构解析策略,共解析了4个杂质的结构,包括已知杂质M和N,还发现了两个新的杂质:丝氨酸(2位)取代的ECBN[ECBN-Ser(2)]和3-羟基-4-羟甲基脯氨酸(6位)取代的ECBN[ECBN-4hMe3-Hyp(6)]。结论本研究为快速、合理解析ECBN或其衍生物中的杂质结构提供了方法,适用于棘白霉素类药物的质量研究。
OBJECTIVE To present a structure analysis strategy for echinocandin B nucleus(ECBN)and the related peptides based on high performance liquid chromatography-quadrupole/time of flight-tandem mass spectrometry(HPLC-Q/TOF-MS/MS).METHODS The characteristic ions of ECBN were analyzed by HPLC-Q/TOF-MS/MS.The proposed fragmentation pathway was based on four series ions,including b ions,y ions and amino acid residue ions.In addition,ECBN contains eight hydroxyl groups,resulting in continuous dehydration ion peaks,which can assist in inferring the structure of ECBN analogues.RESULTS In this paper,a systematic and reasonable structure analysis strategy of ECBN was established for the first time.The structures of four impurities were analyzed,including known impurity M and N.Two new impurities were also analyzed to be ECBN Ser(2),the threonine of position 2 was substituted by serine and ECBN-4hMe3-Hyp(6),the 3-hydroxy-4-methyl-L-proline of position 6 was substituted by 3-hydroxy-4-hydroxymethyl proline.CONCLUSION This study provides a method for rapid and reasonable analyzing the impurity structure in ECBN or its derivatives,which is suitable for the quality control of echinocandins.
作者
张含智
冯震
罗煜
田振华
ZHANG Hanzhi;FENG Zhen;LUO Yu;TIAN Zhenhua(Abiochem Biotechnology Co.,Ltd.,Shanghai 200240,China;Shanghai Institute for Food and Drug Control,Shanghai 201203,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2023年第22期2092-2097,共6页
Chinese Pharmaceutical Journal
