奋乃静在人胆汁中的代谢物分析

Analysis of Perphenazine Metabolites in Human Bile

建立了超高效液相色谱-四极杆串联飞行时间质谱(UPLC/Q-TOF MS)检测并表征奋乃静在人胆汁中代谢物的方法。T管收集一名精神病患者服用奋乃静后的胆汁样品,经乙腈沉淀蛋白预处理后,采用UPLC/Q-TOF MS进行分析。根据高分辨质谱给出的准确分子质量信息推测可能的分子式,结合MSE功能采集的前体离子和产物离子信息,利用质量缺损过滤(MDF)和generic dealkylation等代谢物鉴定软件筛选代谢物。通过对比原形药物和代谢物的质谱裂解途径,推测可能的代谢物结构。在服药(4mg,b.i.d)后的人胆汁中,共检测到29种奋乃静代谢物,包括I相代谢物16种,II相代谢物13种,其中16种为首次报道的新颖代谢物。奋乃静在人体内的主要代谢途径包括羟基化、脱氢、N-去烷基化、甲基化、硫酸及葡萄糖醛酸结合等,该结果进一步完善了奋乃静在人体内的代谢途径。

The detection and characterization of perphenazine metabolites in human bile were performed in this study.After collection from a psychotic patient with T-tube drainage,the bile samples were prepared by acetonitrile-induced protein precipitation and analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC/Q-TOF MS）.According to the elemental compositions deduced from the measured accurate mass and in combination with the precursor and product ions information acquired through the MSE function,the mass defect filter （MDF） technique and generic dealkylation tool were used to eliminate endogenous interferences and screen the metabolites.The structures of the metabolites were elucidated by comparing the fragmentation patterns between the parent drug and metabolites.After twice-daily oral administration of 4 mg of perphenazine to the patient,in addition to the parent drug,29 metabolites,including 16 phase Ⅰ and 13 phase Ⅱ metabolites,were detected and characterized in the patient＇s bile,16 of which had not been previously reported.The major metabolic pathways of perphenazine in human bile include hydroxylation,desaturation,N-dealkylation,methylation,sulfation,and glucuronidation.The results can impove the metabolic pathways of perphenazine in humans.