1. Academic Validation
  2. Quantification of FGFR4 inhibitor BLU-554 in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry

Quantification of FGFR4 inhibitor BLU-554 in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Mar 15;1110-1111:116-123. doi: 10.1016/j.jchromb.2019.02.017.
Burcu Dogan-Topal 1 Wenlong Li 2 Alfred H Schinkel 3 Jos H Beijnen 4 Rolf W Sparidans 5
Affiliations

Affiliations

  • 1 Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands; Ankara University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100 Tandogan, Ankara, Turkey. Electronic address: [email protected].
  • 2 The Netherlands Cancer Institute, Division of Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: [email protected].
  • 3 The Netherlands Cancer Institute, Division of Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: [email protected].
  • 4 Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands; The Netherlands Cancer Institute, Department of Clinical Pharmacology, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: [email protected].
  • 5 Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands; Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Chemical Biology & Drug Development, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands. Electronic address: [email protected].
Abstract

BLU-554 is a potent, highly selective oral FGFR4 Inhibitor. A bioanalytical assay for quantification of BLU-554 in mouse plasma and six tissue homogenates (brain, kidney, liver, lung, small intestine, and spleen) was developed and validated using liquid chromatography with tandem mass spectrometric detection and with erlotinib as internal standard. After protein precipitation with acetonitrile in a 96-well format and separation on an XBridge® Peptide BEH C18 column by gradient elution using 0.2% (v/v) ammonium hydroxide (in water) and methanol, analytes were ionized by positive electrospray and monitored in the selected reaction monitoring mode by triple quadrupole mass spectrometry. The assay was validated in a 1-1000 ng/ml concentration range using calibration in mouse plasma. Precisions (intra-day and inter-day) were in the range 2.8-10.1% and accuracies were in between 88.5 and 96.6% for all levels in all matrices. The assay was successfully applied for a pilot pharmacokinetic and tissue distribution study in wild-type mice.

Keywords

BLU-554; LC-MS/MS; Mouse plasma; Mouse tissue; Pharmacokinetics.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100492
    99.87%, FGFR4 Inhibitor