Prinville, Vivaldy; Ohlund, Leanne et Sleno, Lekha
(2020).
« Targeted Analysis of 46 Bile Acids to Study the Effect of Acetaminophen in Rat by LC-MS/MS ».
Metabolites, 10(1), p. 26.
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Résumé
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 e�ects of di�erent 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 e�ect 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.
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