title: The utility of stable isotope labeled (SIL) analogues in the bioanalysis of endogenous compounds by LC-MS applied to the study of bile acids in a metabolomics assay.
abstract: The growing field of biomarker bioanalysis by liquid chromatography mass spectrometry (LC-MS) is challenged with the selection of suitable matrices to construct relevant and valid calibration curves resulting in not only precise but also accurate data. Because surrogate matrices are often employed with the associated concerns about the accuracy of the obtained data, here we present an assay using surrogate analytes in naive biological matrices. This approach is illustrated with the analysis of endogenous bile acids (e-BAs) in serum and plasma using stable isotope-labeled (SIL) analogues as calibration standards to address the matrix concerns. Several deuterated BAs (d-BAs) were used as standards representing respectively grouped e-BAs with structural similarity allowing for the simultaneous bioanalysis of 16 e-BA. The utility of this LC-MS assay employing d-BAs is demonstrated with the analysis of samples resultant of a controlled metabolomics study where a cohort of rats was fed/fasted to investigate the change of e-BAs dependent on food consumption and fasting time.
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Pennington, NJ 08534, USA.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Zheng
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Wallingford, CT 06492, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Shields
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Wallingford, CT 06492, USA.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Snow
authors.affiliation: Discovery Toxicology, Bristol-Myers Squibb, Princeton, NJ 08543, USA; Applied and Investigational Metabolomics, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Nelson
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Olah
authors.affiliation: Applied and Investigational Metabolomics, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Reily
authors.affiliation: Discovery Toxicology, Bristol-Myers Squibb, Princeton, NJ 08543, USA; Applied and Investigational Metabolomics, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Robertson
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Wallingford, CT 06492, USA; Applied and Investigational Metabolomics, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
authors.forename: Petia A
authors.initials: PA
authors.lastname: Shipkova
authors.affiliation: Discovery Toxicology, Bristol-Myers Squibb, Princeton, NJ 08543, USA; Applied and Investigational Metabolomics, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Stryker
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Pennington, NJ 08534, USA.
authors.forename: Baomin
authors.initials: B
authors.lastname: Xin
authors.affiliation: Bioanalytical Research, Bristol-Myers Squibb, Wallingford, CT 06492, USA. Electronic address: dieter.drexler@bms.com.
authors.forename: Dieter M
authors.initials: DM
authors.lastname: Drexler
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood* / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid; D006801:Humans; D007553:Isotope Labeling; D013058:Mass Spectrometry; D055432:Metabolomics; D015394:Molecular Structure; D051381:Rats
chemical_list: D001647:Bile Acids and Salts
keywords: Bile acids; Deuterated analogues; LC–MS; Naive matrix