d-伪-tocopheryl Polyethylene Glycol 1000 Succinate: A View from FTICR MS and Tandem MS

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• 作者：Juan Wei ; Anthony Bristow ; Eileen McBride ; David Kilgour ; Peter B. O鈥機onnor
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：February 4, 2014
• 年：2014
• 卷：86
• 期：3
• 页码：1567-1574
• 全文大小：314K
• ISSN：1520-6882

文摘

d-伪-tocopheryl polyethylene glycol 1000 succinate (TPGS) is an important polymeric excipient frequently used in drug formulation. However, differing compositions of the TPGS samples between batches are believed to result in variable performance of the formulated product. Herein, a high performance method using Fourier-transform ion cyclotron resonance (FTICR) mass spectrometry (MS) and tandem mass spectrometry (MS/MS) to analyze the composition of TPGS samples and the structure of TPGS was established. Aided by high mass accuracy and high resolution, the full MS overview of TPGS is able to provide composition information, and diagnostic fragments from collisionally activated dissociation (CAD) and electron capture dissociation (ECD) MS/MS can be used for the identification of the TPGS structure. ECD and CAD show different preferences in bond cleavage, and an interesting cross-ring cleavage was generated by CAD. Fragmentation information from ECD/ECD MS³ is useful for providing confidence in the results. The influence of different ionization agents (Na⁺, Li⁺, and Ag⁺) on fragmentation of TPGS was investigated with the silver adduct providing different fragments. In addition to the methodology study, the MS and MS/MS results from four batches of TPGS samples from two manufacturers were compared. This method can be utilized for the composition and structure study of many other polymeric compounds. FTICR MS/MS demonstrated its promising role as a structural characterization tool complementary to traditional spectroscopy techniques.