Wang Yuya, Chen Xiaoyan, Li Qiang, Zhong Dafang
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 646 Songtao Road, Shanghai, China.
J Mass Spectrom. 2008 Aug;43(8):1099-109. doi: 10.1002/jms.1394.
The metabolism of arbidol in humans was studied using liquid chromatography-electrospray ionization (ESI) ion trap mass spectrometry (ITMS) after an oral dose of 300-mg arbidol. A total of 17 metabolites were identified including the glucuronide arbidol and the glucuronide sulfinylarbidol as the major metabolites. Arbidol and its metabolites have some common fragmentation patterns as a result of a homolytic bond cleavage. This cleavage will form odd-electron ions with the loss of a radical. The arbidol fragmentation sequence is first to lose dimethylamine (45 Da), followed by the loss of acetaldehyde (44 Da), and then the phenylthio radical (109 Da). This fragmentation sequence is also observed from N-demethylarbidol, sulfonylarbidol, and N-demethylsulfonylarbidol. However, for sulfinylarbidol and N-demethylsulfinylarbidol, the fragmentation sequence is reversed so that the phenylsulfiny radical (125 Da) was lost first, followed by the loss of dimethylamine (45 Da), and then acetaldehyde (44 Da). The exact masses for arbidol and sulfinylarbidol fragment ions were determined by a quadrupole/time-of-flight mass spectrometer (Q-TOF MS). The phase II metabolites, such as sulfate and glucuronide conjugates of arbidol, N-demethylarbidol, sulfonylarbidol, and N-demethylsulfonylarbidol were identified by observing the neutral loss of 80 Da (SO(3)) or 176 Da (glucuronic acid) from the MS(2) spectra. The sulfate and glucuronide conjugates such as sulfinylarbidol and N-demethylsulfinylarbidol had an unusual fragmentation pattern, in which the phenylsulfinyl radical (125 Da) was lost before the loss of SO(3) group (80 Da) or glucuronic acid (176 Da) occurred.
在口服300毫克阿比朵尔之后，采用液相色谱 - 电喷雾电离（ESI）离子阱质谱（ITMS）研究了阿比朵尔在人体中的代谢情况。共鉴定出17种代谢产物，其中主要代谢产物为阿比朵尔葡萄糖醛酸苷和亚磺酰阿比朵尔葡萄糖醛酸苷。由于均裂键裂解，阿比朵尔及其代谢产物具有一些共同的碎裂模式。这种裂解会形成失去一个自由基的奇电子离子。阿比朵尔的碎裂顺序先是失去二甲胺（45道尔顿），接着失去乙醛（44道尔顿），然后失去苯硫基自由基（109道尔顿）。从N - 去甲基阿比朵尔、磺酰阿比朵尔和N - 去甲基磺酰阿比朵尔中也观察到了这种碎裂顺序。然而，对于亚磺酰阿比朵尔和N - 去甲基亚磺酰阿比朵尔，碎裂顺序相反，先是失去苯亚磺酰基自由基（125道尔顿），接着失去二甲胺（45道尔顿），然后失去乙醛（44道尔顿）。阿比朵尔和亚磺酰阿比朵尔碎片离子的精确质量由四极杆/飞行时间质谱仪（Q - TOF MS）测定。通过观察二级质谱（MS(2)）谱图中80道尔顿（SO(3)）或176道尔顿（葡萄糖醛酸）的中性丢失，鉴定出阿比朵尔、N - 去甲基阿比朵尔、磺酰阿比朵尔和N - 去甲基磺酰阿比朵尔的Ⅱ相代谢产物，如硫酸盐和葡萄糖醛酸结合物。亚磺酰阿比朵尔和N - 去甲基亚磺酰阿比朵尔等硫酸盐和葡萄糖醛酸结合物具有不寻常的碎裂模式，即在失去SO(3)基团（80道尔顿）或葡萄糖醛酸（176道尔顿）之前先失去苯亚磺酰基自由基（125道尔顿）。
