Biomarker discovery for drug-induced phospholipidosis: phenylacetylglycine to hippuric acid ratio in urine and plasma as potential markers

Biomarkers. 2017 Mar;22(2):178-188. doi: 10.1080/1354750X.2016.1252958. Epub 2016 Nov 21.

Abstract

Context: Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment and noninvasive diagnostic tool is highly desirable.

Objective: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach.

Method: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs.

Results: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation.

Conclusion: The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis.

Keywords: Phenylacetylglycine; drug-induced phospholipidosis; hippuric acid; phenylalanine metabolism.

MeSH terms

  • Animals
  • Biomarkers / analysis*
  • Biomarkers / blood
  • Biomarkers / urine
  • Drug Monitoring / methods
  • Glycine / analogs & derivatives*
  • Glycine / analysis
  • Glycine / blood
  • Glycine / urine
  • Hippurates / analysis*
  • Hippurates / blood
  • Hippurates / urine
  • Lipidoses / chemically induced
  • Lipidoses / diagnosis*
  • Metabolomics / methods
  • Phospholipids
  • Rats

Substances

  • Biomarkers
  • Hippurates
  • Phospholipids
  • phenylacetylglycine
  • hippuric acid
  • Glycine