Differentiation of structural isomers in a target drug database by LC/Q-TOFMS using fragmentation prediction
Differentiation of structural isomers in a target drug database by LC/Q-TOFMS using fragmentation prediction
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DOI：
10.1002/dta.134
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发表时间：
2010-05-01
影响因子：
2.9
通讯作者：
Ojanpera, Ilkka
中科院分区：
文献类型：
--
作者：
Tyrkko, Elli;Pelander, Anna;Ojanpera, Ilkka
仅根据化合物的精确质量测量无法区分异构体。使用液相色谱/四极杆飞行时间质谱 (LC/Q-TOFMS) 方法系统地裂解大量不同的异构体。使用两个软件程序来表征化合物的硅质量碎片，以识别特征片段。使用的软件程序是 ACD/MS Fragmenter（ACD Labs Toronto，Canada）和 SmartFormula3D（Bruker Daltonics），前者使用通用破碎规则根据化合物的结构生成片段，后者根据质谱分配片段并使用精确的质量数据计算离子的分子式。从包含 874 种药物的内部毒理学数据库中，发现了包含 111 种化合物的 48 种异构体组，并为其提供了参考标准。使用两个软件程序处理产物离子谱，并为每种化合物鉴定出 1-3 个片段。在 82% 的情况下，两个软件程序都可以识别该片段。只有 10 对异构体无法根据片段进行区分。这些化合物要么是非对映异构体，要么是经历相同断裂的位置异构体。这两个软件程序都可以利用准确的质量数据来阐明片段的结构。平均质量准确度和同位素模式匹配值（SigmaFit；Bruker Daltonics Bremen，德国）分别为 0.9 mDa 和 24.6 mSigma。该研究介绍了一种通过 LC/Q-TOFMS 在大型目标数据库中进行初步化合物鉴定的实用方法，而无需具备参考标准。版权所有 (C) 2010 约翰·威利父子有限公司
Isomers cannot be differentiated from each other solely based on accurate mass measurement of the compound. A liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOFMS) method was used to systematically fragment a large group of different isomers. Two software programs were used to characterize in silico mass fragmentation of compounds in order to identify characteristic fragments. The software programs employed were ACD/MS Fragmenter (ACD Labs Toronto, Canada), which uses general fragmentation rules to generate fragments based on the structure of a compound, and SmartFormula3D (Bruker Daltonics), which assigns fragments from a mass spectra and calculates the molecular formulae for the ions using accurate mass data. From an in-house toxicology database of 874 drug substances, 48 isomer groups comprising 111 compounds, for which a reference standard was available, were found. The product ion spectra were processed with the two software programs and 1-3 fragments were identified for each compound. In 82% of the cases, the fragment could be identified with both software programs. Only 10 isomer pairs could not be differentiated from each other based on their fragments. These compounds were either diastereomers or position isomers undergoing identical fragmentation. Accurate mass data could be utilized with both software programs for structural elucidation of the fragments. Mean mass accuracy and isotopic pattern match values (SigmaFit; Bruker Daltonics Bremen, Germany) were 0.9 mDa and 24.6 mSigma, respectively. The study introduces a practical approach for preliminary compound identification in a large target database by LC/Q-TOFMS without necessarily possessing reference standards. Copyright (C) 2010 John Wiley & Sons, Ltd.