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A rapid methodology for the characterization of dialkyl tertiary amine-n-oxide metabolites using structurally dependent dissociation pathways and reconstructed ion current chromatograms

A rapid methodology for the characterization of dialkyl tertiary amine-n-oxide metabolites using structurally dependent dissociation pathways and reconstructed ion current chromatograms
A rapid methodology for the characterization of dialkyl tertiary amine-n-oxide metabolites using structurally dependent dissociation pathways and reconstructed ion current chromatograms
A high-performance liquid chromatography-electrospray
ionization-tandem mass spectrometry (HPLC-ESI-MS/MS)approach to the characterization of dialkyl tertiary amine-
N-oxides is presented. The methodology is based upon forming reconstructed ion current chromatograms (RICCs)
of m/z values of product ions known to form through diagnostic losses from dialkyl tertiary amine-N-oxides. The
diagnostic losses of N,N-dimethylhydroxylamine and N,Ndiethylhydroxylamine were identified through the analysis of a structurally diverse library of compounds by ESI-lowenergy collision-induced dissociation (CID)-MS/MS using quadrupole ion trap-mass spectrometry (QIT-MS) and quadrupole time-of-flight-mass spectrometry (QqTOF-MS). The
library consisted of dialkyl tertiary amine-containing ommercially available pharmaceuticals, along with a number
of model, synthetic N-oxides. The loss of the nitrogen containing group was observed in 89% of the low-energy CID
product ion spectra acquired using various collision energies.
Further, the resultant product ions, formed through the loss of the nitrogen-containing group, were shown to be
unstable because of the observation of second-generation
dissociation. These observations regarding gas-phase ion
chemistry could be useful to developers of in silico programs for fragmentation prediction by allowing the creation of improved algorithms and models for predicting dissociation.
Using the information derived from the library analysis, the characterization methodology was developed and demonstrated using tetracaine. The approach is rapid, MS/MS
platform independent, utilizes existing technology, and could be automated. Further, it is definitive and overcomes the limitations of other tools for N-oxide identification by localizing the site of oxidation. Thus, it provides a useful addition to the existing approaches for metabolite identification.
0003-2700
2347-2354
Holman, Stephen W.
32d02653-e41d-4615-a660-356fb38b1988
Wright, Patricia
553f5be8-e0fc-41be-ac24-8ffb21cfca82
Langley, G. John
7ac80d61-b91d-4261-ad17-255f94ea21ea
Holman, Stephen W.
32d02653-e41d-4615-a660-356fb38b1988
Wright, Patricia
553f5be8-e0fc-41be-ac24-8ffb21cfca82
Langley, G. John
7ac80d61-b91d-4261-ad17-255f94ea21ea

Holman, Stephen W., Wright, Patricia and Langley, G. John (2010) A rapid methodology for the characterization of dialkyl tertiary amine-n-oxide metabolites using structurally dependent dissociation pathways and reconstructed ion current chromatograms. Analytical Chemistry, 82 (6), 2347-2354. (doi:10.1021/ac902540b).

Record type: Article

Abstract

A high-performance liquid chromatography-electrospray
ionization-tandem mass spectrometry (HPLC-ESI-MS/MS)approach to the characterization of dialkyl tertiary amine-
N-oxides is presented. The methodology is based upon forming reconstructed ion current chromatograms (RICCs)
of m/z values of product ions known to form through diagnostic losses from dialkyl tertiary amine-N-oxides. The
diagnostic losses of N,N-dimethylhydroxylamine and N,Ndiethylhydroxylamine were identified through the analysis of a structurally diverse library of compounds by ESI-lowenergy collision-induced dissociation (CID)-MS/MS using quadrupole ion trap-mass spectrometry (QIT-MS) and quadrupole time-of-flight-mass spectrometry (QqTOF-MS). The
library consisted of dialkyl tertiary amine-containing ommercially available pharmaceuticals, along with a number
of model, synthetic N-oxides. The loss of the nitrogen containing group was observed in 89% of the low-energy CID
product ion spectra acquired using various collision energies.
Further, the resultant product ions, formed through the loss of the nitrogen-containing group, were shown to be
unstable because of the observation of second-generation
dissociation. These observations regarding gas-phase ion
chemistry could be useful to developers of in silico programs for fragmentation prediction by allowing the creation of improved algorithms and models for predicting dissociation.
Using the information derived from the library analysis, the characterization methodology was developed and demonstrated using tetracaine. The approach is rapid, MS/MS
platform independent, utilizes existing technology, and could be automated. Further, it is definitive and overcomes the limitations of other tools for N-oxide identification by localizing the site of oxidation. Thus, it provides a useful addition to the existing approaches for metabolite identification.

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Published date: 15 March 2010

Identifiers

Local EPrints ID: 147635
URI: http://eprints.soton.ac.uk/id/eprint/147635
ISSN: 0003-2700
PURE UUID: 01466161-12d7-4f85-9c07-f36c509a33ea
ORCID for G. John Langley: ORCID iD orcid.org/0000-0002-8323-7235

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Date deposited: 26 Apr 2010 10:21
Last modified: 29 Oct 2019 02:08

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