Isoprostanes are a family of prostaglandin isomers produced from oxidation of polyunsaturated fatty acids through a non-enzymatic free radical-catalyzed mechanism. Quantification of F(2)-isoprostanes (F(2)-IsoPs) provides a good index of oxidative stress and allows non-invasive assessment of lipid peroxidation in vivo. Since "interferences peaks" at m/z 573 co-elute with d(4)-15-F(2t)-IsoP preferentially used, we propose a new GC-NICI-MS approach to quantify urinary F(2)-IsoPs by using 4(RS)-F(4t)-neuroprostane as the internal standard. This method was applied to quantify urinary F(2)-IsoPs excretion in healthy volunteers and polytraumatized patients. Our results showed a significant increase (p<0.0001) in urinary F(2)-IsoPs in polytraumatized patients compared with healthy volunteers (4.73+/-2.75 ng/mg vs. 0.811+/-0.359 ng/mg creatinine).