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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/1/26 |
| _version_ | 1819021140519026688 |
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| author | Vivaldy Prinville Leanne Ohlund Lekha Sleno |
| author_facet | Vivaldy Prinville Leanne Ohlund Lekha Sleno |
| author_sort | Vivaldy Prinville |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T04:02:22Z |
| format | Article |
| id | doaj.art-2847b6505899429dba6a1488fbc18772 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-12-21T04:02:22Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-2847b6505899429dba6a1488fbc187722022-12-21T19:16:40ZengMDPI AGMetabolites2218-19892020-01-011012610.3390/metabo10010026metabo10010026Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MSVivaldy Prinville0Leanne Ohlund1Lekha Sleno2Department of Chemistry, Université du Québec à Montréal (UQAM), P.O. Box 8888 Downtown Station, Montreal, QC H3C 3P8, CanadaDepartment of Chemistry, Université du Québec à Montréal (UQAM), P.O. Box 8888 Downtown Station, Montreal, QC H3C 3P8, CanadaDepartment of Chemistry, Université du Québec à Montréal (UQAM), P.O. Box 8888 Downtown Station, Montreal, QC H3C 3P8, CanadaBile 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.https://www.mdpi.com/2218-1989/10/1/26bile acidsmetabolomicsrat plasmatandem mass spectrometryliquid chromatographyacetaminophenhepatotoxicity |
| spellingShingle | Vivaldy Prinville Leanne Ohlund Lekha Sleno Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS Metabolites bile acids metabolomics rat plasma tandem mass spectrometry liquid chromatography acetaminophen hepatotoxicity |
| title | Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS |
| title_full | Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS |
| title_fullStr | Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS |
| title_full_unstemmed | Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS |
| title_short | Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS |
| title_sort | targeted analysis of 46 bile acids to study the effect of acetaminophen in rat by lc ms ms |
| topic | bile acids metabolomics rat plasma tandem mass spectrometry liquid chromatography acetaminophen hepatotoxicity |
| url | https://www.mdpi.com/2218-1989/10/1/26 |
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