Flow-Injection MS/MS for Gas-Phase Chiral Recognition and Enantiomeric Quantitation of a Novel Boron-Containing Antibiotic (GSK2251052A) by the Mass Spectrometric Kinetic Method
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- 作者：Lianming Wu ; Frederick G. Vogt ; David Q. Liu
- 刊名：Analytical Chemistry
- 出版年：2013
- 出版时间：May 21, 2013
- 年：2013
- 卷：85
- 期：10
- 页码：4869-4874
- 全文大小：343K
- 年卷期：v.85,no.10(May 21, 2013)
- ISSN：1520-6882
文摘
The present work demonstrates, for the first time, the application of the mass spectrometric kinetic method for quantitative chiral purity determination by automatic flow-injection MS/MS. The particular compound analyzed is GSK2251052A, a novel boron-containing systemic antibiotic for the treatment of multidrug-resistant Gram-negative bacterial infections. Chiral recognition and quantitation of GSK2251052A was achieved based on the competitive dissociation kinetics of the CuII-bound trimeric complex [CuII(A)(ref*)2鈥揌]+ (A = GSK2251052A or its R-enantiomer, ref* = l-tryptophan) that gives rise to CuII-bound dimeric complexes. The sensitive nature of the methodology and the linear relationship between the logarithm of the fragment ion abundance ratio and the optical purity, characteristic of the kinetic method, allow chiral purity determination of pharmaceutical compounds during enantioselective synthesis. By using flow-injection MS/MS, enantiomeric quantitation of GSK2251052A by the kinetic method proved to be fast (2 min for analysis of each sample) and to have accuracy comparable to chiral LC鈥揗S/MS and LC鈥揢V methods as well as the method using chiral derivatization followed by LC鈥揗S/MS analysis. This flow-injection MS/MS method represents an alternative approach to commonly used chromatographic techniques as a means of chiral purity determination and is particularly useful for rapid screening of chiral drugs during pharmaceutical development.