Rapid and Robust Quantification of p-Xyleneselenocyanate in Plasma via Derivatization

5 years ago

Rapid and Robust Quantification of p-Xyleneselenocyanate in Plasma via Derivatization

Ying Zhao, Maria Angels Subirana, Tobias Ginman, Manuchehr Abedi-Valugerdi, Brigitte Twelkmeyer, Fadwa Benkessou, Håkan Ottosson, Wenyi Zheng, Siyao Wang, Moustapha Hassan

p-Xyleneselenocyanate (p-XSC) is one of the most investigated selenium compounds in cancer-prevention and -therapy. Despite the potent anticancer property, there is still no proper method to perform the quantitative analysis of p-XSC in plasma. In this investigation, we aimed at developing a method based on liquid chromatography–mass spectrometry (LC-MS) for the measurement of p-XSC in plasma. Direct deproteinization was first used to extract parent p-XSC from plasma, but failed to achieve high recovery rate (<2%) due to formation of selenium–sulfur bond between p-XSC and plasma protein. To overcome this problem, we modified the extraction method to three steps: (1) break the selenium–sulfur bond by tris(2-carboxyethyl)phosphine; (2) stabilize the newly formed intermediate selenol by N-ethylmaleimide; (3) deproteinization. This three-step method efficiently recovered bound p-XSC by more than 75%. In in vivo study, p-XSC was injected intravenously into mice and plasma was collected for LC-MS analysis. Consistently, p-XSC was undetectable in its parent form, whereas the bound form was readily quantified, employing the modified extraction method. In summary, we describe a novel, robust, and sensitive method for quantification of p-XSC in plasma. The present method will enable pharmacokinetic and pharmacodynamic studies of p-XSC in both clinical and preclinical settings.

Publisher URL: http://dx.doi.org/10.1021/acs.analchem.7b01426

DOI: 10.1021/acs.analchem.7b01426