A multiplex HRMS assay for quantifying selected human plasma bile acids as candidate OATP biomarkers

Bioanalysis. 2018 May 1;10(9):645-657. doi: 10.4155/bio-2017-0274. Epub 2018 May 11.

Abstract

Aim: Selected bile acids (BAs) in plasma have been proposed as endogenous probes for assessing drug-drug interactions involving hepatic drug transporters such as the organic anion-transporting polypeptides (OATP1B1 and OATP1B3).

Materials & methods: Plasma extracts were analyzed for selected BAs using a triple TOF API6600 high-resolution mass spectrometer.

Results: Glycodeoxycholic acid 3-sulfate, glycochenodeoxycholic acid 3-sulfate, glycodeoxycholic acid 3-O-β-glucuronide and glycochenodeoxycholic acid 3-O-β-glucuronide are presented as potential OATP1B1/3 biomarkers.

Conclusion: Six BAs are quantified in human plasma using a multiplexed high-resolution mass spectrometry method. Glycodeoxycholic acid 3-sulfate and glycodeoxycholic acid 3-O-β-glucuronide are proposed as potential biomarkers based on observed four- to fivefold increase in plasma AUC (vs placebo), following administration of a compound known to present as an OATP1B1/3 inhibitor in vitro.

Keywords: HRMS; bile acids; biomarkers; organic anion-transporting polypeptide.

MeSH terms

  • Area Under Curve
  • Biomarkers, Pharmacological / blood*
  • Chromatography, Liquid
  • Drug Interactions
  • Female
  • Glycodeoxycholic Acid / analogs & derivatives
  • Glycodeoxycholic Acid / blood*
  • Humans
  • Liver-Specific Organic Anion Transporter 1 / metabolism*
  • Male
  • Mass Spectrometry / methods
  • Pharmaceutical Preparations / metabolism
  • Sensitivity and Specificity
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / metabolism*

Substances

  • Biomarkers, Pharmacological
  • Liver-Specific Organic Anion Transporter 1
  • Pharmaceutical Preparations
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Glycodeoxycholic Acid