2种芳香化酶抑制剂和3种5型磷酸二酯酶抑制剂的电喷雾四极杆飞行时间质谱裂解规律研究

Fragmentation rules of 2 aromatase inhibitors and 3 phosphodiesterase-5 inhibitors with electrospray ionization quadrupole time-of-flight mass spectrometry

目的研究2种芳香化酶抑制剂(AIs)阿那曲唑和来曲唑以及3种5型磷酸二酯酶抑制剂(PDE5Is)西地那非、N-去甲基西地那非和他达拉非的质谱裂解规律。方法采用高分辨电喷雾四极杆飞行时间质谱(ESI-Q-TOF/MS)正离子模式检测5个化合物,解析其准分子离子和特征碎片离子的相对分子质量信息,研究质谱裂解规律。结果5个化合物均易加合H+离子形成[M+H]^(+)准分子离子。在二级碰撞诱导解离过程中,阿那曲唑和来曲唑均先脱三氮唑中性碎片,再脱CH_(3)自由基或HCN;西地那非和N-去甲基西地那非的裂解途径基本一致,但在低质量区的特征碎片离子存在差异;他达拉非易经新的途径裂解,先脱OH自由基,再裂解得到集中于低质量区的特征碎片。结论AIs和PDE5Is的质谱裂解分别具有各自的规律,他达拉非易经新的途径裂解,该研究可为两类酶抑制剂的结构解析及药效评价提供参考。

Objective To explore the fragmentation rules of 2 aromatase inhibitors(AIs,including anastrozole and letrozole)and 3 phosphodiesterase-5(PDE5)inhibitors(PDE5Is,including sildenafil,N-desmethylsildenafil and tadalafil).Methods High-resolution electrospray ionization quadrupole time-of-flight mass spectrometry(ESI-Q-TOF/MS)in a positive ion mode was used to analyze the relative molecular mass information of the quasi-molecular ions and the characteristic fragment ions of the 5 compounds,and to determine their fragmentation rules.Results All 5 compounds were prone to being protonated and forming[M+H]^(+)quasi-molecular ion peaks.During the collisioninduced dissociation,both anastrozole and letrozole first brove away from triazole,and then CH_(3) free radicals or HCN.The fragmentation pathways of sildenafil and N-desmethylsildenafil were basically the same,with difference in the characteristic fragment ions in the low-mass region.Tadalafil tended to dissociate OH free radicals in a new fragmentation pathway and then cracked into characteristic fragment ions in the low-mass region.Conclusion The fragmentation of 2 AIs and 3 PDE5Is show their own characteristics,and tadalafil splits through a new pathway.This study provides references for structure analysis and pharmacodynamic evaluation of two types of enzyme inhibitors.