6种他汀类药物的电喷雾离子阱质谱分析

采用电喷雾离子阱多级质谱技术对6种他汀类药物进行系统研究,总结了该类化合物的电喷雾质谱断裂规律。根据主要药效基团存在形式的不同,分两类解析。第一类:辛伐他汀和洛伐他汀在正离子模式下发生β,δ-二羟基戊内酯开环断裂,生成中性丢失H2O、CO、CH3COOH的碎片离子;第二类:普伐他汀和阿托伐他汀在负离子模式下产生脱去104 u(3-羟基-1,4-丁內酯和H2)和160 u(3,5-二羟基-1,7-庚内酯)的碎片离子;氟伐他汀和瑞舒伐他汀在负离子模式下产生脱去62 u(CO2和H2O)的碎片离子,对该二级碎片离子进行三级全扫描质谱分析,产生脱去42 u(CH2=C=O)和96 u(环已烯-3-酮)的碎片离子。这些质谱特征有助于他汀类药物的结构分析和鉴定。

Analysis of Six Statins by Electrospray Ion Trap Mass Spectrometry

To investigate the fragmentation mechanism of statins, six statins were studied by electrospray ionization-ion trap mass spectrometry (ESI-MSⁿ). Based on the forms of the main pharmacophore, the samples were analyzed into two groups. The first group, including simvastatin and lovastatin, which were detected in positive ion mode. It is indicated that most fragments are produced after neutral loss processes such as elimination of 18 u (H₂O), 28 u (CO) and 60 u (CH₃COOH) following the ring opening of the lactone. The second goup including pravastatin, atorvastatin, fluvastatin and rosuvastatin were invesgated in negative ion mode. It is observed that the main fragments are derived from neutral losses of 104 u (3-hydroxy-1,4-butyrolactone and H₂) and 160 u (3,5-dihydroxy-1,7-heptalactone) of pravastatin and atorvastatin. While losses of 62 u (CO₂ and H₂O) of fluvastatin and rosuvastatin are detected. And further losses of 42 u (CH₂=C=O) and 96 u (cyclohexen-3-one) are observed in MS³.These characteristics can be used for future structural analysis and identification in studies of statins and analogue compounds.