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Rapid analysis of pharmaceuticals and excreted xenobiotic and endogenous metabolites with atmospheric pressure infrared MALDI mass spectrometry

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Abstract

Atmospheric pressure (AP) infrared (IR) matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) was demonstrated for the rapid direct analysis of pharmaceuticals, and excreted human metabolites. More than 50 metabolites and excreted xenobiotics were directly identified in urine samples with high throughput. As the water content of the sample was serving as the matrix, AP IR-MALDI showed no background interference in the low mass range. The structure of targeted ions was elucidated from their fragmentation pattern using collision activated dissociation. The detection limit for pseudoephedrine was found to be in the sub-femtomole range and the semi-quantitative nature of the technique was tentatively demonstrated for a metabolite, fructose, by using a homologous internal standard, sucrose. A potential application of AP IR-MALDI for intestinal permeability studies was also explored using polyethylene glycol.

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Abbreviations

AP:

Atmospheric pressure

IR:

Infrared

MALDI:

Matrix-assisted laser desorption/ionization (MALDI)

MS:

Mass spectrometry

DESI:

Desorption electrospray ionization

DART:

Direct analysis in real time

DAPCI:

Desorption atmospheric pressure chemical ionization

LAESI:

Laser ablation electrospray ionization

DIOS:

Desorption ionization on silicon

LISMA:

Laser-induced silicon microcolumn arrays

CAD:

Collision activated dissociation

LOD:

Limit of detection

m/z :

Mass-to-charge ratio

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Acknowledgements

The authors would like to recognize the financial support from the W. M. Keck Foundation (041904), the U.S. Department of Energy (DEFG02-01ER15129), and the George Washington University Research Enhancement Fund for this work. Modified capillary inlets for the mass spectrometer were kindly provided by D. Kenny of the Waters Co.

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  1. Department of Chemistry, W. M. Keck Institute for Proteomics Technology and Applications, George Washington University, Washington, DC, 20052, USA

    Bindesh Shrestha, Yue Li & Akos Vertes

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  1. Bindesh Shrestha
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  2. Yue Li
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Correspondence to Akos Vertes.

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Shrestha, B., Li, Y. & Vertes, A. Rapid analysis of pharmaceuticals and excreted xenobiotic and endogenous metabolites with atmospheric pressure infrared MALDI mass spectrometry. Metabolomics 4, 297–311 (2008). https://doi.org/10.1007/s11306-008-0120-8

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