title: Improved synthesis of glycine, taurine and sulfate conjugated bile acids as reference compounds and internal standards for ESI-MS/MS urinary profiling of inborn errors of bile acid synthesis.
abstract: Bile acid synthesis defects are rare genetic disorders characterized by a failure to produce normal bile acids (BAs), and by an accumulation of unusual and intermediary cholanoids. Measurements of cholanoids in urine samples by mass spectrometry are a gold standard for the diagnosis of these diseases. In this work improved methods for the chemical synthesis of 30 BAs conjugated with glycine, taurine and sulfate were developed. Diethyl phosphorocyanidate (DEPC) and diphenyl phosphoryl azide (DPPA) were used as coupling reagents for glycine and taurine conjugation. Sulfated BAs were obtained by sulfur trioxide-triethylamine complex (SO3-TEA) as sulfating agent and thereafter conjugated with glycine and taurine. All products were characterized by NMR, IR spectroscopy and high resolution mass spectrometry (HRMS). The use of these compounds as internal standards allows an improved accuracy of both identification and quantification of urinary bile acids.
authors.affiliation: Institute of Pediatric Research "Città della Speranza", Corso Stati Uniti 4, 35127, Padova, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Donazzolo
authors.affiliation: Institute of Pediatric Research "Città della Speranza", Corso Stati Uniti 4, 35127, Padova, Italy. Electronic address: antonina.gucciardi@unipd.it.
authors.forename: Antonina
authors.initials: A
authors.lastname: Gucciardi
authors.affiliation: Department of Chemical Science, University of Padova, Via Marzolo 1, 35131, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mazzier
authors.affiliation: Department of Chemical Science, University of Padova, Via Marzolo 1, 35131, Padova, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Peggion
authors.affiliation: Women's and Children's Health Department, University of Padova, Via Giustiniani 3, 35128, Padova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Pirillo
authors.affiliation: Women's and Children's Health Department, University of Padova, Via Giustiniani 3, 35128, Padova, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Naturale
authors.affiliation: Department of Chemical Science, University of Padova, Via Marzolo 1, 35131, Padova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretto
authors.affiliation: Women's and Children's Health Department, University of Padova, Via Giustiniani 3, 35128, Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giordano
mesh_terms: D001647:Bile Acids and Salts / Q000138:chemical synthesis / Q000592:standards / Q000652:urine*; D005998:Glycine / Q000737:chemistry* / Q000592:standards; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000652:urine*; D008968:Molecular Conformation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D013431:Sulfates / Q000737:chemistry* / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards; D013654:Taurine / Q000737:chemistry* / Q000592:standards
chemical_list: D001647:Bile Acids and Salts; D013431:Sulfates; D013654:Taurine; D005998:Glycine
keywords: Bile acid sulfates synthesis; ESI–MS/MS; Glycine conjugated synthesis; Inborn error defects; Liver disease; Taurine conjugated synthesis