Simultaneous determination of FL118 and W34 in rat Blood by LC-MS/MS: Application to pharmacokinetic studies

Biomed Chromatogr. 2020 Nov;34(11):e4944. doi: 10.1002/bmc.4944. Epub 2020 Jul 21.

Abstract

W34 is a prodrug of FL118, and it can be converted to FL118 via a hydrolysis reaction. In this report, a highly sensitive LC-MS/MS method using a C18 column was validated and used for the simultaneous determination of W34 and FL118 in rat blood. A stepwise gradient elution with 0.1% formic acid in water and acetonitrile was employed. The assays were linear over a concentration range of 0.50-50.0 ng/ml for both W34 and FL118. The accuracy of the validation method ranged from 89.74 to 98.94% for W34 and from 88.61 to 94.60% for FL118. The precision was within 7.15% for W34 and 9.63% for FL118. Extraction recoveries of W34 were 94.56-100.49 and 87.67-106.32% for FL118. No significant matrix effects for both W34 and FL118 were observed in blood. The assay has been successfully applied to biological samples obtained from a stability and pharmacokinetic study of W34 and FL118.

Keywords: FL118; LC-MS/MS; W34; camptothecin; pharmacokinetics.

MeSH terms

  • Animals
  • Benzodioxoles / blood*
  • Benzodioxoles / chemistry
  • Benzodioxoles / pharmacokinetics*
  • Camptothecin
  • Chromatography, Liquid / methods*
  • Indolizines / blood*
  • Indolizines / chemistry
  • Indolizines / pharmacokinetics*
  • Limit of Detection
  • Linear Models
  • Male
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*

Substances

  • 7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione
  • Benzodioxoles
  • Indolizines
  • Camptothecin