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Quantitative profiling of bile acids in biofluids and tissues based on accurate mass high resolution LC-FT-MS: Compound class targeting in a metabolomics workflow

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Author: Bobeldijk, I. · Hekman, M. · Vries de- Weij, J.van der · Coulier, L. · Ramaker, R. · Kleemann, R. · Kooistra, T. · Rubingh, C. · Freidig, A. · Verheij, E.
Type:article
Date:2008
Institution: TNO Kwaliteit van Leven
Source:Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 2, 871, 306-313
Identifier: 240956
doi: doi:10.1016/j.jchromb.2008.05.008
Keywords: Analytical research · Accurate mass · Bile acids · Body fluids · High performance liquid chromatography · Metabolomics · Targeted metabolite profiling · Tissues · Acids · Arsenic compounds · Chlorine compounds · Cholesterol · Chromatographic analysis · Complexation · Electrospray ionization · Fourier transforms · High performance liquid chromatography · Histology · Ionization · Ionization of liquids · Liquid chromatography · Liquid phase epitaxy · Liver · Mass spectrometers · Mass spectrometry · Metabolites · Phase separation · Plasmas · Separation · Spectrometers · Spectrometry · Sulfate minerals · Accurate mass · Bile acid synthesis · Bile acids · Bio-fluids · Biological fluids · Cholesterol homeostasis · Chromatography-mass spectrometry · Electro spraying · Fourier Transform Mass Spectrometer · Generic methods · High resolutions · HPLC-MS · Human plasmas · Human urine · Linear ion trap · Metabolomics · Mouse liver · Pooled samples · Reversed-phase high performance · Sample preparations · Targeted metabolite profiling · Tissues · Body fluids · Bile acid · Glycine · Sulfate · Accuracy · Animal experiment · Animal tissue · Article · Bile acid synthesis · Body fluid · Cholesterol intake · Cholesterol liver level · Controlled study · Electrospray · Fourier transform mass spectrometry · Homeostasis · Human · Liver · Metabolite · Metabolomics · Nonhuman · Priority journal · Quantitative analysis · Reversed phase high performance liquid chromatography · Statistical significance · Tissue · Animals · Bile Acids and Salts · Cholesterol, Dietary · Chromatography, Liquid · Computational Biology · Fourier Analysis · Humans · Liver · Mass Spectrometry · Metabolism · Mice · Reproducibility of Results

Abstract

We report a sensitive, generic method for quantitative profiling of bile acids and other endogenous metabolites in small quantities of various biological fluids and tissues. The method is based on a straightforward sample preparation, separation by reversed-phase high performance liquid-chromatography mass spectrometry (HPLC-MS) and electrospray ionisation in the negative ionisation mode (ESI-). Detection is performed in full scan using the linear ion trap Fourier transform mass spectrometer (LTQ-FTMS) generating data for many (endogenous) metabolites, not only bile acids. A validation of the method in urine, plasma and liver was performed for 17 bile acids including their taurine, sulfate and glycine conjugates. The method is linear in the 0.01-1 μM range. The accuracy in human plasma ranges from 74 to 113%, in human urine 77 to 104% and in mouse liver 79 to 140%. The precision ranges from 2 to 20% for pooled samples even in studies with large number of samples (n > 250). The method was successfully applied to a multi-compartmental APOE*3-Leiden mouse study, the main goal of which was to analyze the effect of increasing dietary cholesterol concentrations on hepatic cholesterol homeostasis and bile acid synthesis. Serum and liver samples from different treatment groups were profiled with the new method. Statistically significant differences between the diet groups were observed regarding total as well as individual bile acid concentrations. © 2008 Elsevier B.V. All rights reserved.