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Bioanalytical assay for quantifying FGFR4 inhibitor BLU 554


Fibroblast growth factor 19 (FGF19) is a hormone-like receptor that is mainly found in mature hepatocytes. It is involved in liver homeostasis, by interacting with fibroblast growth factor receptor 4 (FGFR4) and has been identified as a driver of hepatocellular carcinoma (HCC). The (FGFR4) inhibitor BLU 554 is currently undergoing phase I and II clinical trials for the treatment of HCC. To date, no bioanalytical assays have been developed for the quantification of BLU 554. This study developed a chromatographic LC-MS/MS-based assay for the quantification of BLU 554 (from Carbosynth - BB160379) in mouse plasma and in six different tissue homogenates.

The developed assay includes an initial pre-treatment step with acetonitrile for protein precipitation, which enhances sample throughput in a 96-well plate format. The xBridge® Peptide BEH C18 column was used for chromatographic separation. Analytes were ionized with positive electrospray, set for the single protonated BLU 554 (m/z 432.1), and quantified at m/z 485.1. Erlotinib was used as the internal standard, following a screen of compounds with chromatographic properties resembling BLU 554. 

The validity, precision and accuracy of the method was tested, which met the requirements of international guidelines. The protocol was also used to study the pharmacokinetics and tissue distribution of BLU 554 in mice. Thus, this first LC-MS/MS method can be applied in further studies in mice, which will be beneficial for future pre-clinical and clinical studies.  

For further information, please refer to the original paper: Dogan-Topal et al, 2019.

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