奋乃静在人胆汁中的代谢物分析

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MS E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（4 mg,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。     

UPLC/Q-TOFMS鉴定人参皂苷Rh2在大鼠体内的代谢产物

An ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) was used for the identification of metabolites in rats after oral administration of ginsenoside Rh2. The plasma, bile, urine and feces samples were collected after single oral administration of 50 mg•kg^－1 Rh2 to rats. The samples were prepared by protein precipitation with acetonitrile. After comparison with the blank samples, identification of the metabolites and their structural elucidation were performed by investigating their accurate mass data, and product ion spectra obtained from positive and negative ion detection mode using MSE data collection function(where E represents collision energy). The results reveal that the major metabolic pathways of Rh2 include deglycosylation, oxygenation, desaturation and sulfate conjugation. Protopanaxadiol is detected in rat feces. Neither parent compound nor metabolites are found in rat urine. Glutathione adduct of Rh2 is found as one of the major metabolites in rat bile, and cysteine-adduct metabolites are detected in feces. These results are helpful for the understanding of Rh2 metabolism in rat.     

UPLC/Q-TOFMSE法快速鉴定奋乃静在人胆汁中的代谢物

The metabolites of perphenazine in human bile were rapid investigated employing UPLC/Q-TOF MS^E (where E represents energy) technique. The bile samples were collected after dosing to human and purified through acetonitrile protein precipitation. Data collection was done by UPLC/Q-TOF MS^E. According to the molecule formular educed from the measured accurate mass, mass defect filter(MDF) technique and generic dealkylation tool were used to screen the metabolites. Their structures were elicited by comparing the fragmentation patterns between parent drug and metabolites. All the metabolites has chlorine atom isotope cluster. After oral administration of perphenazine to the patient, 29 metabolites including 16 phase I and 13 phase II metabolites are detected in human bile. The major metabolic pathways of perphenazine in human are hydroxylation, N-dealkylation, desaturation, sulfation and glucuronate conjugation.     

液相色谱-串联质谱法检测反应性代谢物

已有报道一些药物进入体内后在各种代谢酶的作用下转化为反应性代谢物,然后与生物大分子（如蛋白、DNA）共价结合,导致毒性。在药物发现和开发阶段进行反应性代谢物筛查,对上市药物进行反应性代谢物监测已经成为一个重要的研究领域。通常,反应性代谢物具有亲电性,能被小分子亲核试剂（如谷胱甘肽及其衍生物、氰离子、胺类等）体外捕获,采用液相色谱 串联质谱法检测并鉴定这些结合物的结构是研究反应性代谢物的基本方法。本文综述了液相色谱与不同质谱仪联用（三重四极杆、离子阱、四极杆-线性离子阱、高分辨质谱仪）检测反应性代谢产物的方法以及应用进展。