Determination of a PDE4 inhibitor Hemay005 in human plasma and urine by UPLC-MS/MS and its application to a PK study

Bioanalysis. 2018 Jun 1;10(11):863-875. doi: 10.4155/bio-2018-0004. Epub 2018 Jun 4.

Abstract

Aim: Hemay005 is a novel small-molecule inhibitor of phosphodiesterase-4 developed for the treatment of psoriasis. Measurement of Hemay005 in biological samples is critical for evaluation of its pharmacokinetics in clinical studies. Methodology & results: Plasma and urine samples were extracted and then chromatographed on an Acquity UPLC HSS T3 column with a gradient elution. Detection was performed on a Xevo TQ-S tandem mass spectrometer using negative ESI.

Conclusion: For the first time, a sensitive and robust ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the quantitative determination of Hemay005 in human plasma and urine, and it was successfully applied to evaluate the pharmacokinetics of Hemay005 in healthy subjects in a first-in-human study.

Keywords: Hemay005; UPLC–MS/MS; first-in-human; human plasma; human urine; pharmacokinetics; psoriasis.

MeSH terms

  • Acetamides / blood*
  • Acetamides / pharmacokinetics
  • Acetamides / urine*
  • Analytic Sample Preparation Methods
  • Blood Chemical Analysis / methods*
  • Chromatography, High Pressure Liquid / methods*
  • Humans
  • Phosphodiesterase 4 Inhibitors / blood
  • Phosphodiesterase 4 Inhibitors / pharmacokinetics
  • Phosphodiesterase 4 Inhibitors / urine
  • Pyrroles / blood*
  • Pyrroles / pharmacokinetics
  • Pyrroles / urine*
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*
  • Thiophenes / blood*
  • Thiophenes / pharmacokinetics
  • Thiophenes / urine*
  • Urinalysis / methods*

Substances

  • Acetamides
  • Hemay005
  • Phosphodiesterase 4 Inhibitors
  • Pyrroles
  • Thiophenes
  • acetamide