A Simple LC-MS/MS Method for the Quantification of PDA-66 in Human Plasma

Molecules. 2022 Feb 1;27(3):974. doi: 10.3390/molecules27030974.

Abstract

The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine-threonine kinase glycogen synthase kinase 3β SB216763, has shown preclinical antitumour effects in various cell lines, with the key pathways of its anticancer activity being cell cycle modulation, DNA replication and p53 signalling. For the monitoring of anticancer drug treatment in the context of therapeutic drug monitoring, the determination of plasma concentrations is essential, for which an LC-MS/MS method is particularly suitable. In the present study, a sensitive LC-MS/MS method for the quantification of the potential anticancer drug PDA-66 in human plasma with a lower limit of quantification of 2.5 nM is presented. The method was successfully validated and tested for the determination of PDA-66 in mouse plasma and sera.

Keywords: LC-MS/MS; PDA-66; human plasma; liquid–liquid extraction; validation.

MeSH terms

  • Animals
  • Antineoplastic Agents / blood*
  • Chromatography, Liquid / methods*
  • Humans
  • Indoles / blood*
  • Limit of Detection
  • Maleimides / blood*
  • Mice
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*

Substances

  • Antineoplastic Agents
  • Indoles
  • Maleimides
  • PDA-66