苯胺基喹唑啉类酪氨酸激酶抑制剂的电喷雾质谱裂解规律

Fragmentation Pathways of Tyrosine Kinase Inhibitors With Anilinoquinazoline Moiety by Electrospray Ionization Mass Spectrometry

研究吉非替尼、厄洛替尼和艾克替尼3种苯胺基喹唑啉类酪氨酸激酶抑制剂,在电喷雾质谱正离子模式下的裂解规律.通过电喷雾质谱产生各化合物稳定的[M+H]^+准分子离子峰,进而对[M+H]^+离子进行高能诱导裂解和碰撞诱导裂解,获得相应化合物的质谱图.结果表明:在电喷雾电离(ESI)多级质谱中,3种药物的裂解主要发生在喹唑啉环C_4,C_6和C_7位取代基上,并伴随分子内重排和H+的迁移重排;在二级质谱图中,吉非替尼的高丰度特征离子质荷比(m/z)为128.1,厄洛替尼的m/z值为278.1和336.1,埃克替尼的m/z值为278.1,304.1.

The fragmentation pathways of three tyrosine kinase inhibitors with anilinoquinazoline moiety including gefitinib,erlotinib and icotinibwere analyzed by electrospray ionization tandem mass spectrometry in positive ion mode.The[M＋H]＋ions peaks were generated by electrospray ionization tandem mass spectrometry,and the subsequent product ions of [M＋H]＋ ions information were obtained by using the higher energy collision induced dissociation and the collision induced dissociation.The results indicate that the fragmentation behavior mainly results from the cleavage of the C4,C6 and C7 substituent of the quinazoline ring,with intramolecular rearrangement and migration rearrangement of H＋,and the high-abundance characteristic ions for gefitinib is m/z=128.1,for erlotinib are m/z=278.1 and m/z=336.1,and for icotinib are m/z=278.1 and m/z=304.1 in the secondary mass spectrum.