Preliminary Study Of The Acute Radiation Injury Early Triage Based On Amino Acids Target Analysis

Rapid radiation injury early triage for large-scale people after radiation exposure isvital for limited medical resources allocation and early treatment of a large number ofwounded after nuclear accident. In this thesis, a high performance liquidchromatography electrospay tandem mass spectrometry (HPLC-ESI-MS/MS) methodwas developed for the analysis of amino acids in rat body fluids firstly. Then thistechnology platform was applied to investigate the effect of acute ionizing radiation onamino acids in rat body fluids from the dose and time effects. Finally, the radiationinjury triage was studied combined with non-linear partial least squares (PLS).1) A robust and sensitive liquid chromatography/electrospray tandem massspectrometry (HPLC-ESI-MS/MS) method of coupling solid phase extraction (SPE)sample preparation was developed and optimized for quantification of various aminoacids in rat plasma and urine. Silica-based strong cationic exchange SPE cartridges wereused to extract amino acids and minimize the ion-suppression effect. The SPE cleanupprotocol was optimized and it was found that the sample loading pH was very critical toget satisfactory recoveries and reproducible data. When the sample was mixed with0.1mol/L acetic acid (pH2.8) and then loaded with an SPE cartridge, the recoveries andrepeatability for most of the amino acids were satisfactory. In addition, the analysismethod characteristics including precision, accuracy and standard curve wereinvestigated.2) The analytical plasma amino acids platform was applied to investigate the effectof acute ionizing radiation on amino acids in rat plasma from the dose and time effects.Then, the radiation injury triage was studied combined with non-linear partial leastsquares (PLS). The classification accuracy of without radiation exposure was92.3%at5h after radiation. At24h after radiation, the triage accuracies were all above83%in thedifferent doses of irradiated groups, the correct classification rates of moderate andsevere radiation injury were91.7%and92.3%respectively. At72h after radiation, the classification accuracies of all levels of radiation injury were more than90%, the correctclassification rates of moderate and severe groups were up to100%.3) The analytical urine amino acids platform was applied to investigate the effectof acute ionizing radiation on amino acids in rat urine from the dose and time effects.Then, the radiation injury triages were studied combined with non-linear partial leastsquares (PLS). The results showed that injury classifications were better at48h and72hafter radiation, the correct classification rates of different levels of radiation injury wereabove70%. In general, the triage results of urine samples were inferior to plasmasamples.