title: Application of isotope-based carboxy group derivatization in LC-MS/MS analysis of tissue free-fatty acids for thyroid carcinoma.
abstract: Free fatty acids (FFAs) analysis of human tissue is challenging due to the low abundance of tissue lipids and interference from the complex matrix. Based on our previously reported on 2,4-dimethoxy-6-piperazin-1-yl pyrimidine (DMPP) derivatization toward carboxy group, we have further applied DMPP derivatization method in the assay of tissue FFAs in patients with thyroid carcinoma after method optimization including sample pretreatment, and derivatization condition. d6-DMPP labeled mixture of FFAs standard was used as the internal standard (IS). The d0-DMPP labeled samples (spiked with IS) were subsequently used for lipids profiling by selective reaction monitoring (SRM) detection. The DMPP derivatization combined with SRM not only allowed trace analysis of FFAs in complex matrix due to the extremely high sensitivity, but also minimized the errors in quantitation because of the very similar property between d0-DMPP derivatized samples and d6-DMPP derivatized IS. Eighteen kinds of FFAs were detected successfully with the increased level in carcinoma tissue compared with the normal tissue, which may be the results of abnormality in the metabolism of fatty acid synthases and lipids. Application of the DMPP based FFAs derivatization is expected to provide a promising tool for the investigation of lipids in vivo, especially for the research of lipid metabolism.
authors.affiliation: Shanghai Mass Spectrometry Center, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 200032 Shanghai, China.
authors.forename: Jiapeng
authors.initials: J
authors.lastname: Leng
authors.forename: Qing
authors.initials: Q
authors.lastname: Guan
authors.forename: Tuanqi
authors.initials: T
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Wu
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Cao
authors.forename: Yinlong
authors.initials: Y
authors.lastname: Guo
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D004246:Dimethylphenylpiperazinium Iodide / Q000737:chemistry; D005230:Fatty Acids, Nonesterified / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D007554:Isotopes / Q000737:chemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D005230:Fatty Acids, Nonesterified; D007554:Isotopes; D008055:Lipids; D004246:Dimethylphenylpiperazinium Iodide
keywords: Derivatization; Free fatty acid; Isotope labeling; LC–MS/MS; Thyroid carcinoma