Abstract:As the selenium (Se) levels in the serum are critical to human health, it is imperative to develop highly sensitive analytical methods for determining the content of Se in the serum. Although using O2 as a reaction gas in the MS/MS mode can effectively eliminate spectral interference, the sensitivity for determining Se remains low with the use of inductively coupled plasma tandem-mass spectrometry (ICP-MS/MS). In this study, a new strategy of using ICP-MS/MS to determine the trace Se level in human serum containing gadolinium (Gd)-based magnetic resonance imaging (MRI) contrasting agents was proposed. In the MS/MS mode, N2O was used as the reaction gas, N atom transfer reaction between N2O and Se+ was adopted, and SeN+ was selected as the detection ion to eliminate all mass spectrometric interferences, including Gd++. The accuracy and precision of the analytical method were evaluated by using standard reference materials. The results obtained indicated that interference-free determination of the Se level can be achieved by using high abundance isotopes 80Se and 78Se in the N2O reaction mode. The sensitivity of Se was higher when compared to that of the case in the conventional O2 reaction mode. The limit of detection (LOD) was set as low as 2.19 ng L-1 (for the most-abundant Se isotope). The RSD was 2.5%–4.2%, and the spiking recovery was 94.8%–106%. The proposed method is simple and practical, with high sensitivity and good accuracy and precision. The present study offers not only a precise and dependable approach for the highly sensitive detection of Se level in human serum containing gadolinium (Gd)-based MRI contrast agents but also introduces a novel concept for designing an N2O-reaction mode to eliminate spectral interference, thereby enabling the wider application of Se detection across various fields.