title: Benzylic rearrangement stable isotope labeling for quantitation of guanidino and ureido compounds in thyroid tissues by liquid chromatography-electrospray ionization mass spectrometry.
abstract: Benzylic rearrangement stable isotope labeling (BRSIL) was explored to quantify the guanidino and ureido compounds (GCs and UCs). This method employed a common reagent, benzil, to label the guanidino and ureido groups through nucleophilic attacking then benzylic migrating. The use of BRSIL was investigated in the analysis of five GCs (creatine, l-arginine, homoarginine, 4-guanidinobutyric acid, and methylguanidine) and two UCs (urea and citrulline). The labeling was found simple and specific. The introduction of bi-phenyl group and the generation of nitrogen heterocyclic ring in the benzil-d0/d5 labeled GCs and UCs improved the retention behaviors in liquid chromatography (LC) and increased the sensitivity of electrospray ionization mass spectrometry (ESI MS) detection. The fragment ion pairs of m/z 182/187 and m/z 210/215 from the benzil-d0/d5 tags facilitated the discovery of potential GCs and UCs candidates residing in biological matrices. The use of BRSIL combined with LC-ESI MS was applied for simultaneously quantitation of GCs and UCs in thyroid tissues. It was demonstrated that nine GCs and UCs were detected, six of which were further quantified based on corresponding standards. It was concluded that five GCs and UCs (l-arginine, homoarginine, 4-guanidinobutyric acid, methylguanidine, and citrulline) were statistically significantly different (p < 0.05) between the para-carcinoma and carcinoma thyroid tissue samples.
authors.affiliation: State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People's Republic of China.
authors.forename: Ruo-Jing
authors.initials: RJ
authors.lastname: Fan
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People's Republic of China. Electronic address: fzhang@sioc.ac.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People's Republic of China.
authors.forename: Jia-Peng
authors.initials: JP
authors.lastname: Leng
authors.affiliation: Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, People's Republic of China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People's Republic of China. Electronic address: tuanqisun@163.com.
authors.forename: Tuan-Qi
authors.initials: TQ
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Organmetallic Chemistry and National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, People's Republic of China. Electronic address: ylguo@sioc.ac.cn.
authors.forename: Yin-Long
authors.initials: YL
authors.lastname: Guo
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D006146:Guanidines / Q000032:analysis*; D007553:Isotope Labeling; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013961:Thyroid Gland / Q000737:chemistry*; D014508:Urea / Q000032:analysis*
chemical_list: D006146:Guanidines; D014508:Urea
keywords: Benzylic rearrangement; Guanidino group; Liquid chromatography-mass spectrometry; Stable isotope; Thyroid tissue; Ureido group