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J Am Soc Mass Spectrom. 2018 Aug;29(8):1650-1664. doi: 10.1007/s13361-018-1977-z. Epub 2018 May 7.

Differential Mobility Spectrometry-Mass Spectrometry (DMS-MS) in Radiation Biodosimetry: Rapid and High-Throughput Quantitation of Multiple Radiation Biomarkers in Nonhuman Primate Urine.

Author information

1
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
2
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA. Steve.Coy@post.harvard.edu.
3
Tumor Biology Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 20057, USA.
4
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, 20057, USA.
5
Department of Oncology, Georgetown University Medical Center, Washington, DC, 20057, USA.
6
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA. P.Vouros@northeastern.edu.
7
Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, 02115, USA. P.Vouros@northeastern.edu.

Abstract

High-throughput methods to assess radiation exposure are a priority due to concerns that include nuclear power accidents, the spread of nuclear weapon capability, and the risk of terrorist attacks. Metabolomics, the assessment of small molecules in an easily accessible sample, is the most recent method to be applied for the identification of biomarkers of the biological radiation response with a useful dose-response profile. Profiling for biomarker identification is frequently done using an LC-MS platform which has limited throughput due to the time-consuming nature of chromatography. We present here a chromatography-free simplified method for quantitative analysis of seven metabolites in urine with radiation dose-response using urine samples provided from the Pannkuk et al. (2015) study of long-term (7-day) radiation response in nonhuman primates (NHP). The stable isotope dilution (SID) analytical method consists of sample preparation by strong cation exchange-solid phase extraction (SCX-SPE) to remove interferences and concentrate the metabolites of interest, followed by differential mobility spectrometry (DMS) ion filtration to select the ion of interest and reduce chemical background, followed by mass spectrometry (overall SID-SPE-DMS-MS). Since no chromatography is used, calibration curves were prepared rapidly, in under 2 h (including SPE) for six simultaneously analyzed radiation biomarkers. The seventh, creatinine, was measured separately after 2500× dilution. Creatinine plays a dual role, measuring kidney glomerular filtration rate (GFR), and indicating kidney damage at high doses. The current quantitative method using SID-SPE-DMS-MS provides throughput which is 7.5 to 30 times higher than that of LC-MS and provides a path to pre-clinical radiation dose estimation. Graphical Abstract.

KEYWORDS:

Biomarkers; DMS-MS; Differential mobility spectrometry; FAIMS-MS; Field asymmetric waveform ion mobility spectrometry; Metabolomics; Nonhuman primate; Quantitation; Radiation exposure

PMID:
29736597
PMCID:
PMC6287943
DOI:
10.1007/s13361-018-1977-z
[Indexed for MEDLINE]
Free PMC Article

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