Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS
Bile acids represent a large class of steroid acids synthesized in the liver and further metabolized by many bacterial and mammalian enzymes. Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to study the variation of individual circulatin...
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| Veröffentlicht in: | Metabolites 2020-01, Vol.10 (1), p.26, Article 26 |
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| creator | Prinville, Vivaldy Ohlund, Leanne Sleno, Lekha |
| description | Bile acids represent a large class of steroid acids synthesized in the liver and further metabolized by many bacterial and mammalian enzymes. Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to study the variation of individual circulating bile acids in the context of hepatotoxity or liver disease. Acetaminophen (APAP), a drug commonly taken to relieve pain and decrease fever, is known to cause acute liver failure at high doses. We have developed a targeted liquid chromatography-tandem mass spectrometry method to monitor the effects of different doses of APAP on the bile acid plasma profile in a rat model. The analysis method was optimized to ensure chromatographic resolution of isomeric species using a mixture of 46 standard bile acids, and 14 isotopically-labeled internal standard (IS) compounds detected in multiple reaction monitoring (MRM) mode on a triple quadrupole mass spectrometer. Four doses of acetaminophen were studied, the highest of which shows signs of hepatotoxicity in rats. This targeted method revealed that high dose APAP has an important effect on bile acid profiles. Changes were seen in several unconjugated bile acids as well as glycine conjugates; however, no obvious changes were apparent for taurine-conjugated species. |
| doi_str_mv | 10.3390/metabo10010026 |
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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 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Variations in bile acid levels can be used as a measure of liver function. There still exists, however, a need to study the variation of individual circulating bile acids in the context of hepatotoxity or liver disease. Acetaminophen (APAP), a drug commonly taken to relieve pain and decrease fever, is known to cause acute liver failure at high doses. We have developed a targeted liquid chromatography-tandem mass spectrometry method to monitor the effects of different doses of APAP on the bile acid plasma profile in a rat model. The analysis method was optimized to ensure chromatographic resolution of isomeric species using a mixture of 46 standard bile acids, and 14 isotopically-labeled internal standard (IS) compounds detected in multiple reaction monitoring (MRM) mode on a triple quadrupole mass spectrometer. Four doses of acetaminophen were studied, the highest of which shows signs of hepatotoxicity in rats. This targeted method revealed that high dose APAP has an important effect on bile acid profiles. Changes were seen in several unconjugated bile acids as well as glycine conjugates; however, no obvious changes were apparent for taurine-conjugated species.</description><subject>Acetaminophen</subject><subject>Acids</subject><subject>Analgesics</subject><subject>Apoptosis</subject><subject>Bile</subject><subject>Bile acids</subject><subject>Biochemistry & Molecular Biology</subject><subject>Cholesterol</subject><subject>Chromatography</subject><subject>Drug dosages</subject><subject>Fever</subject><subject>Hepatotoxicity</subject><subject>Life Sciences & Biomedicine</subject><subject>Liquid chromatography</subject><subject>Liver</subject><subject>Liver diseases</subject><subject>Mass spectroscopy</subject><subject>Metabolism</subject><subject>metabolomics</subject><subject>Plasma</subject><subject>rat plasma</subject><subject>Science & Technology</subject><subject>tandem mass spectrometry</subject><subject>Taurine</subject><issn>2218-1989</issn><issn>2218-1989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNks1rFDEUwAdRbKm9epSAF0GmTWbyeRG2Q9XCFsGtFy8hX7ObZWayTjLK_vdm3Lp0PRkCCckvv_fCe0XxGsGruhbwundJ6YAgzLOiz4rzqkK8RIKL50_2Z8VljFuYB4WEQfSyOKuRqCnE9Xnx_UGNa5ecBYtBdfvoIwgtwBTc-M6BhfE2ghTAKk12D9LGgdu2dSbN0MLk8L0fwm7jBuAH8FUloPdg2ZT3q-v71aviRau66C4f14vi28fbh-Zzufzy6a5ZLEuDOU4lbknOjBJModHEGSuI5shwpi2n0AmLscFMESEYVq1FqkVUIUQNVQYrAuuL4u7gtUFt5W70vRr3Migv_xyEcS3VmLzpnKw4ZpoSSLgQuBJWq6zCnLfaIM5YlV0fDq7dpHtnjRvSqLoT6enN4DdyHX5KBquKYpYF7x4FY_gxuZhk76NxXacGF6Yoq7rmgjPO51hv_0G3YRpzFTJFsICCEzYLrw6UGUOMo2uPySAo5y6Qp12QH7x5-oUj_rfmGXh_AH45HdpovBuMO2K5TQiqIWLV3DFzlvz_6cYnlXwYmjANqf4NK1rLZA</recordid><startdate>20200107</startdate><enddate>20200107</enddate><creator>Prinville, Vivaldy</creator><creator>Ohlund, Leanne</creator><creator>Sleno, Lekha</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-7923-8019</orcidid></search><sort><creationdate>20200107</creationdate><title>Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS</title><author>Prinville, Vivaldy ; 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| source | DOAJ Directory of Open Access Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acetaminophen Acids Analgesics Apoptosis Bile Bile acids Biochemistry & Molecular Biology Cholesterol Chromatography Drug dosages Fever Hepatotoxicity Life Sciences & Biomedicine Liquid chromatography Liver Liver diseases Mass spectroscopy Metabolism metabolomics Plasma rat plasma Science & Technology tandem mass spectrometry Taurine |
| title | Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS |
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