Simultaneous characterization of bile acids and their sulfate metabolites in mouse liver, plasma, bile, and urine using LC-MS/MS

Jiangeng Huang, Sai Praneeth R. Bathena, Iván L. Csanaky, Yazen Alnouti

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Sulfation is a major metabolic pathway involved in the elimination and detoxification of bile acids (BAs). Several lines of evidence are available to support the role of sulfation as a defensive mechanism to attenuate the toxicity of accumulated BAs during hepatobiliary diseases. Individual BAs and their sulfate metabolites vary markedly in their physiological roles as well as their toxicities. Therefore, analytical techniques are required for the quantification of individual BAs and BA-sulfates in biological fluids and tissues. Here we report a simple, sensitive, and validated LC-MS/MS method for the simultaneous quantification of major BAs and BA-sulfates in mouse liver, plasma, bile, and urine. One-step sample preparation using solid-phase extraction (for bile and urine) or protein precipitation (for liver and plasma) was used to extract BAs and BA-sulfates. Base-line separation of all analytes (unsulfated- and sulfated BAs) was achieved in 25. min with a limit of quantification of 1. ng/ml. This LC-MS/MS method was applied to simultaneously quantify BAs and BA-sulfates in both male and female mouse tissues and fluids. Less than 3% of total BAs are present in the sulfate form in the mouse liver, plasma, and bile, which provides strong evidence that sulfation is a minor metabolic pathway of BA elimination and detoxification in mice. Furthermore, we report that the marked female-predominant expression of Sult2a1 is not reflected into a female-predominant pattern of BA-sulfation.

Original languageEnglish (US)
Pages (from-to)1111-1119
Number of pages9
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume55
Issue number5
DOIs
StatePublished - Jul 15 2011

Fingerprint

Metabolites
Bile Acids and Salts
Bile
Liver
Urine
Plasmas
Detoxification
Metabolic Networks and Pathways
Toxicity
bile acid sulfates
Tissue
Fluids
Solid Phase Extraction
Sulfates

Keywords

  • Bile acids
  • Gender difference
  • LC-MS/MS
  • Mouse
  • Sulfation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

Simultaneous characterization of bile acids and their sulfate metabolites in mouse liver, plasma, bile, and urine using LC-MS/MS. / Huang, Jiangeng; Bathena, Sai Praneeth R.; Csanaky, Iván L.; Alnouti, Yazen.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 55, No. 5, 15.07.2011, p. 1111-1119.

Research output: Contribution to journalArticle

@article{1438e0b0ef9047c088930010c3559909,
title = "Simultaneous characterization of bile acids and their sulfate metabolites in mouse liver, plasma, bile, and urine using LC-MS/MS",
abstract = "Sulfation is a major metabolic pathway involved in the elimination and detoxification of bile acids (BAs). Several lines of evidence are available to support the role of sulfation as a defensive mechanism to attenuate the toxicity of accumulated BAs during hepatobiliary diseases. Individual BAs and their sulfate metabolites vary markedly in their physiological roles as well as their toxicities. Therefore, analytical techniques are required for the quantification of individual BAs and BA-sulfates in biological fluids and tissues. Here we report a simple, sensitive, and validated LC-MS/MS method for the simultaneous quantification of major BAs and BA-sulfates in mouse liver, plasma, bile, and urine. One-step sample preparation using solid-phase extraction (for bile and urine) or protein precipitation (for liver and plasma) was used to extract BAs and BA-sulfates. Base-line separation of all analytes (unsulfated- and sulfated BAs) was achieved in 25. min with a limit of quantification of 1. ng/ml. This LC-MS/MS method was applied to simultaneously quantify BAs and BA-sulfates in both male and female mouse tissues and fluids. Less than 3{\%} of total BAs are present in the sulfate form in the mouse liver, plasma, and bile, which provides strong evidence that sulfation is a minor metabolic pathway of BA elimination and detoxification in mice. Furthermore, we report that the marked female-predominant expression of Sult2a1 is not reflected into a female-predominant pattern of BA-sulfation.",
keywords = "Bile acids, Gender difference, LC-MS/MS, Mouse, Sulfation",
author = "Jiangeng Huang and Bathena, {Sai Praneeth R.} and Csanaky, {Iv{\'a}n L.} and Yazen Alnouti",
year = "2011",
month = "7",
day = "15",
doi = "10.1016/j.jpba.2011.03.035",
language = "English (US)",
volume = "55",
pages = "1111--1119",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",
number = "5",

}

TY - JOUR

T1 - Simultaneous characterization of bile acids and their sulfate metabolites in mouse liver, plasma, bile, and urine using LC-MS/MS

AU - Huang, Jiangeng

AU - Bathena, Sai Praneeth R.

AU - Csanaky, Iván L.

AU - Alnouti, Yazen

PY - 2011/7/15

Y1 - 2011/7/15

N2 - Sulfation is a major metabolic pathway involved in the elimination and detoxification of bile acids (BAs). Several lines of evidence are available to support the role of sulfation as a defensive mechanism to attenuate the toxicity of accumulated BAs during hepatobiliary diseases. Individual BAs and their sulfate metabolites vary markedly in their physiological roles as well as their toxicities. Therefore, analytical techniques are required for the quantification of individual BAs and BA-sulfates in biological fluids and tissues. Here we report a simple, sensitive, and validated LC-MS/MS method for the simultaneous quantification of major BAs and BA-sulfates in mouse liver, plasma, bile, and urine. One-step sample preparation using solid-phase extraction (for bile and urine) or protein precipitation (for liver and plasma) was used to extract BAs and BA-sulfates. Base-line separation of all analytes (unsulfated- and sulfated BAs) was achieved in 25. min with a limit of quantification of 1. ng/ml. This LC-MS/MS method was applied to simultaneously quantify BAs and BA-sulfates in both male and female mouse tissues and fluids. Less than 3% of total BAs are present in the sulfate form in the mouse liver, plasma, and bile, which provides strong evidence that sulfation is a minor metabolic pathway of BA elimination and detoxification in mice. Furthermore, we report that the marked female-predominant expression of Sult2a1 is not reflected into a female-predominant pattern of BA-sulfation.

AB - Sulfation is a major metabolic pathway involved in the elimination and detoxification of bile acids (BAs). Several lines of evidence are available to support the role of sulfation as a defensive mechanism to attenuate the toxicity of accumulated BAs during hepatobiliary diseases. Individual BAs and their sulfate metabolites vary markedly in their physiological roles as well as their toxicities. Therefore, analytical techniques are required for the quantification of individual BAs and BA-sulfates in biological fluids and tissues. Here we report a simple, sensitive, and validated LC-MS/MS method for the simultaneous quantification of major BAs and BA-sulfates in mouse liver, plasma, bile, and urine. One-step sample preparation using solid-phase extraction (for bile and urine) or protein precipitation (for liver and plasma) was used to extract BAs and BA-sulfates. Base-line separation of all analytes (unsulfated- and sulfated BAs) was achieved in 25. min with a limit of quantification of 1. ng/ml. This LC-MS/MS method was applied to simultaneously quantify BAs and BA-sulfates in both male and female mouse tissues and fluids. Less than 3% of total BAs are present in the sulfate form in the mouse liver, plasma, and bile, which provides strong evidence that sulfation is a minor metabolic pathway of BA elimination and detoxification in mice. Furthermore, we report that the marked female-predominant expression of Sult2a1 is not reflected into a female-predominant pattern of BA-sulfation.

KW - Bile acids

KW - Gender difference

KW - LC-MS/MS

KW - Mouse

KW - Sulfation

UR - http://www.scopus.com/inward/record.url?scp=79956062293&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956062293&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2011.03.035

DO - 10.1016/j.jpba.2011.03.035

M3 - Article

VL - 55

SP - 1111

EP - 1119

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

IS - 5

ER -