Validated UPLC-MS/MS method for quantification of fruquintinib in rat plasma and its application to pharmacokinetic study

Abstract

A new, simple, and sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification of fruquintinib was established to assess the pharmacokinetics of fruquintinib in the rat. The internal standard working solution was added to the plasma sample for extraction before analysis. The Acquity UPLC BEH C18 chromatography column (2.1 mm ×50 mm, 1.7 μm) was used to separated analytes under gradient elution using acetonitrile and 0.1% formic acid as the mobile phase. Positive multiple reaction monitoring modes were chosen to detect fruquintinib and diazepam (IS). The precursor-to-product ion transitions were 394.2 → 363.2 for fruquintinib and m/z 285 → 154 for IS. The current method was linear over the concentration range of 1.0–1000 ng/mL for fruquintinib with a correlation coefficient of 0.9992 or better. The matrix effect of fruquintinib and IS was acceptable under the current method. The intra- and interday precision (RSD%) and accuracy (RE%) were within 11.9% and ±13.7%, respectively. The recovery, stability, and sensitivity were validated according to the United States Food and Drug Administration (FDA) regulations for bioanalytical method validation. The analytical method had been validated and applied to a pharmacokinetic study of fruquintinib in rat.

Keywords:

• fruquintinib
• UPLC-MS/MS
• rat plasma
• pharmacokinetics

Acknowledgment

This work was supported by the First Affiliated Hospital of Wenzhou Medical University (FHY2015019).

Abbreviations

UPLC-MS/MS, ultraperformance liquid chromatography-tandem mass spectrometry; LLOQ, lower limit of quantification; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; CFDA, China Food and Drug Administration; NSCLC, non-small-cell lung cancer; CRC, colorectal cancer; QCs, quality control sample; LC-MS/MS, liquid chromatography-tandem mass spectrometry; m/z, precursor-to-product ion transitions of fruquintinib.

Disclosure

The authors report no conflicts of interest in this work.