Molecular Formula Analysis by an MS/MS/MS Technique To Expedite Dereplication of Natural Products

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• 作者：Yasuo Konishi ; Taira Kiyota ; Cristina Draghici ; Jin-Ming Gao ; Faustinus Yeboah ; Stephane Acoca ; Suwatchai Jarussophon ; Enrico Purisima
• 刊名：Analytical Chemistry
• 出版年：2007
• 出版时间：February 1, 2007
• 年：2007
• 卷：79
• 期：3
• 页码：1187 - 1197
• 全文大小：395K
• 年卷期：v.79,no.3(February 1, 2007)
• ISSN：1520-6882

文摘

A facile and sensitive mass spectrometric method hasbeen developed for the dereplication of natural products.The method provides information about the molecularformula and substructure of a precursor molecule and itsfragments, which are invaluable aids in dereplication ofnatural products at their early stages of purification andcharacterization. Collision-induced MS/MS technique isused to fragment a precursor ion into several productions, and individual product ions are selected and subjected to collision-induced MS/MS/MS analysis. Thismethod enables the identification of the fragmentationpathway of a precursor molecule from its first-generationfragments (MS/MS), through to the nth generation product ions (MSⁿ). It also allows for the identification of thecorresponding neutral products released (neutral losses).Elements used in the molecular formula analysis includeC, H, N, O, and S, as most natural products are constituted by these five elements. High-resolution mass separation and accurate mass measurements afforded theunique identification of molecular formula of small neutralproducts. Through sequential add-up of the molecularformulas of the small neutral products, the molecularformula of the precursor ion and its productions wereuniquely determined. The molecular formula of the precursor molecule was then reversely used to identify orconfirm the molecular formula of the neutral products andthat of the productions. The molecular formula of theneutral fragments allowed for the identification of substructures, leading to a rapid and efficient characterizationof precursor natural product. The method was applied topaclitaxel (C₄₇H₅₁NO₁₄; 853 amu) to identify its molecularformula and its substructures, and to characterize itspotential fragmentation pathways. The method was furthervalidated by correctly identifying the molecular formulaof minocycline (C₂₃H₂₇N₃O₇; 457 amu) and piperacillin(C₂₃H₂₇N₅O₇S; 517 amu).