Liquid chromatography/tandem mass spectrometry utilizing ion-molecule reactions and collision-activated dissociation for the identification of N-oxide drug metabolites

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• 作者：Steven C. Habicht ; Penggao Duan ; Nelson R. Vinueza ; Mingkun Fu ; Hilkka I. Kenttä ; maa
• 关键词：Liquid chromatography/mass spectrometry (LC/MS) ; Tandem mass spectrometry (MSⁿ) ; N-oxide ; Ion-molecule reactions ; Structural elucidation
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2010
• 出版时间：11 March 2010
• 年：2010
• 卷：51
• 期：4
• 页码：805-811
• 全文大小：521 K

文摘

A liquid chromatography/tandem mass spectrometry (LC/MS³) method based on ion-molecule reactions and collision-activated dissociation (CAD) is presented for the identification of analytes with the N-oxide functional group directly in mixtures. Tri(dimethylamino)borane (TDMAB) rapidly and selectively derivatizes protonated N-oxides in a modified commercial linear quadrupole ion trap (LQIT) mass spectrometer to yield a distinct product ion (adduct—(CH₃)₂NH). The LQIT was outfitted with an external reagent-mixing manifold that allows TDMAB to be mixed with the helium buffer gas used in the trap. The derivatized analytes are readily identified on the basis of a shift of 98 Th (Thomson) relative to the m/z value of the protonated analyte. Further probing of the derivatized analytes via isolation followed by CAD can be used to confirm the presence of an N-oxide, and distinguish between aliphatic and aromatic tertiary N-oxides. Since the ion-molecule reaction is fast, these experiments can be accomplished on the same time scale as typical CAD-based MSⁿ experiments, thus maintaining the duty cycle of the instrument for this type of experiment. To demonstrate real world applicability, the method was tested on real active pharmaceutical ingredients and their derivatives.