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J Am Soc Mass Spectrom. 2016 Oct;27(10):1626-36. doi: 10.1007/s13361-016-1438-5. Epub 2016 Jul 8.

Rapid and High-Throughput Detection and Quantitation of Radiation Biomarkers in Human and Nonhuman Primates by Differential Mobility Spectrometry-Mass Spectrometry.

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Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, 20057, USA.
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 20057, USA.
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 22254, Saudi Arabia.
Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, 02115, USA.
Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, 02115, USA.


Radiation exposure is an important public health issue due to a range of accidental and intentional threats. Prompt and effective large-scale screening and appropriate use of medical countermeasures (MCM) to mitigate radiation injury requires rapid methods for determining the radiation dose. In a number of studies, metabolomics has identified small-molecule biomarkers responding to the radiation dose. Differential mobility spectrometry-mass spectrometry (DMS-MS) has been used for similar compounds for high-throughput small-molecule detection and quantitation. In this study, we show that DMS-MS can detect and quantify two radiation biomarkers, trimethyl-L-lysine (TML) and hypoxanthine. Hypoxanthine is a human and nonhuman primate (NHP) radiation biomarker and metabolic intermediate, whereas TML is a radiation biomarker in humans but not in NHP, which is involved in carnitine synthesis. They have been analyzed by DMS-MS from urine samples after a simple strong cation exchange-solid phase extraction (SCX-SPE). The dramatic suppression of background and chemical noise provided by DMS-MS results in an approximately 10-fold reduction in time, including sample pretreatment time, compared with liquid chromatography-mass spectrometry (LC-MS). DMS-MS quantitation accuracy has been verified by validation testing for each biomarker. Human samples are not yet available, but for hypoxanthine, selected NHP urine samples (pre- and 7-d-post 10 Gy exposure) were analyzed, resulting in a mean change in concentration essentially identical to that obtained by LC-MS (fold-change 2.76 versus 2.59). These results confirm the potential of DMS-MS for field or clinical first-level rapid screening for radiation exposure. Graphical Abstract ᅟ.


Biomarkers; DMS-MS; Differential mobility spectrometry; FAIMS-MS; Field asymmetric waveform ion mobility spectrometry; Gamma radiation; Human; Nonhuman primates; Radiation exposure

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