A high-throughput liquid chromatography-tandem mass spectrometry assay for the simultaneous quantification of p -cresol sulfate, p -cresol glucuronide, indoxyl-sulfate, and indoxyl glucuronide in HepaRG culture medium and the demonstration of mefenamic acid as a potent and selective detoxifying agent

p-cresol and indole are diet-derived uremic compounds which undergo sulfonation to generate the highly toxic p-cresol sulfate (pCS) and indoxyl sulfate (IxS). They are also subjected to glucuronidation to produce the less toxic p-cresol glucuronide (pCG) and indoxyl glucuronide (IG). We developed and validated a liquid chromatography-mass spectrometry assay to quantify these metabolites in the HepaRG model. We also tested the effects of mefenamic acid, a noncompetitive sulfotransferase inhibitor, on the in-situ formations of these metabolites in relation to the development of cellular necrosis.