Structural elucidation of metabolites of ritonavir and indinavir by liquid chromatography-mass spectrometry
Structural elucidation of metabolites of ritonavir and indinavir by liquid chromatography-mass spectrometry
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DOI：
10.1016/s0021-9673(02)01243-8
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发表时间：
2002-10-18
影响因子：
4.1
通讯作者：
Vouros, P
中科院分区：
文献类型：
--
作者：
Gangl, E;Utkin, I;Vouros, P
利托那韦和茚地那韦，艾滋病病毒蛋白酶抑制剂药物的代谢产物的结构解析，液相色谱-电喷雾电离质谱法进行了描述。利托那韦和茚地那韦分别通过与移植质量人肝微粒体孵育进行生物转化。然后通过与离子阱（ITMS）偶联的HPLC和三重四极杆质量分析仪分析孵育混合物。代谢产物保留了母体分子的大部分结构特征。通过梯度洗脱HPLC对同量异位物质进行基线色谱分离，可以快速鉴定这些代谢产物的结构。这两种药物主要通过氧化和水解途径生物转化为许多代谢产物，这些代谢产物保留了母体分子的许多特征。三重四极杆和离子阱质谱法联合应用，以彻底检测和彻底表征这些代谢产物。此外，保留时间和数据依赖性扫描确保了详细的MS-MS光谱的采集，用于利托那韦和茚地那韦代谢途径的快速检测。ITMS和三重四极杆数据的比较显示质谱模式的定性和定量差异，表明这些仪器应平行使用，以确保通过LC-MS进行全面的代谢物检测和表征。（C）2002 Elsevier Science B. V.保留所有权利。
The structural elucidation of metabolites of ritonavir and indinavir, HIV-protease inhibitor drugs, by liquid chromatography-electrospray ionization mass spectrometry is described. Ritonavir and indinavir were biotransformed separately by incubation with transplant quality human liver microsomes. The incubation mixture was then analyzed by HPLC coupled to ion trap (ITMS) and triple quadrupole mass analyzers. The metabolites retained most of the structural features of the parent molecules. Baseline chromatographic resolution of isobaric species by gradient elution HPLC permitted rapid structural identification of these metabolites. Both drugs were biotransformed primarily by oxidative and hydrolytic pathways to numerous metabolites that retained many of the features of the parent molecules. Triple quadrupole and ion trap mass spectrometry were applied jointly to thoroughly detect and thoroughly characterize these metabolites. Furthermore, retention-time and data-dependent scanning assured acquisition of detailed MS-MS spectra for rapid detection of metabolic pathways of ritonavir and indinavir. Comparison of the ITMS and triple quadrupole data showed qualitative and quantitative differences in the mass spectral patterns, suggesting that these instruments should be used in parallel to ensure comprehensive metabolite detection and characterization by LC-MS. (C) 2002 Elsevier Science B.V. All rights reserved.