电喷雾四极杆飞行时间质谱研究紫杉醇类药物的裂解规律  

Fragmentation behaviors of taxanes drugs using electrospray ionization with quadrupole time-of-flight mass spectrometry

作　　者：马文晓[1] 王浩[1] 王婷婷[2] 杨艳[1] 顾景凯[1,2] 

机构地区：[1]吉林大学药物代谢研究中心,吉林长春130012 [2]吉林大学白求恩第一医院临床药理中心,吉林长春130061

出　　处：《药学学报》2013年第12期1812-1816,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30973587)

摘　　要：采用高质量准确度、高分辨率的Q-TOF研究了在电喷雾正离子模式下含有紫杉烷二萜基本骨架的两种紫杉醇类药物的质谱裂解行为。通过ESI-MS产生的[M+H]+获得相应化合物的相对分子质量信息,对[M+H]+进行碰撞诱导解离(collisional-induced dissociation,CID),以质子化准分子离子[M+H]+作为内标物,对碎片离子进行准确质量测定,确认这些碎片离子的元素组成,获得相应化合物的裂解途径信息。研究发现,结构类似的紫杉醇和多烯紫杉醇具有相似的电喷雾质谱行为,侧链与紫杉烷环连接处的C-O键易断裂,之后脱去二萜骨架上的取代基,并形成m/z 105.033 7、291.137 3、309.148 5、327.159 7、387.181 2和509.217 4等共同碎片,这些特征可为紫杉醇类药物的体内外定性和定量研究提供依据。The fragmentation pathways of two taxanes drugs have been studied in positive ion mode by Q-TOF with the advantages of high mass accuracy and high resolution analysis. The [M＋H] ＋ ions were observed by ESI-MS, from which the molecular weights were obtained. Using the protonated pseudo-molecular ions [M＋H]＋ as internal reference compounds, the accurate mass and element composition of the fragment ions were determined. The collision induced dissociation （CID） data of the [M＋H] ＋ ions provided fragmentation pathways of related compounds. Results showed that the major cleavage pathways of paclitaxel and docetaxel were the same that the cleavage of C-O bond between the side chain and taxol skeleton easily occurred, then stripping of the functional groups on the parent ring. Some common fragments were formed, such as m/z 105.033 7, 291.137 3, 309.148 5, 327.159 7, 387.181 2 and 509.217 4, which would provide a basis for future qualitative and quantitative analysis of taxanes in vitro and in vivo.

关 键 词：紫杉醇 多烯紫杉醇 电喷雾 四级杆-飞行时间质谱 正离子模式 

分 类 号：R917[医药卫生—药物分析学]