The Quantification of Paclitaxel and Its Two Major Metabolites in Biological Samples by HPLC-MS/MS and Its Application in a Pharmacokinetic and Tumor Distribution Study in Xenograft Nude Mouse

Molecules. 2023 Jan 19;28(3):1027. doi: 10.3390/molecules28031027.

Abstract

A rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the quantification of Paclitaxel (PTX), 6α-hydroxypaclitaxel (6α-OHP), and p-3'-hydroxypaclitaxel (3'-OHP) in mouse plasma and tumor tissue. The analytes were separated using a C18 column (50 × 2.1 mm, 1.8 μm), and a triple-quadrupole mass spectrometry device equipped with an electrospray ionization (ESI) source was applied for their detection. PTX, 6α-OHP, and 3'-OHP were extracted from the biological samples with the solid-phase extraction cartridge. The method was fully validated according to the FDA's guidance. The method was linear over the concentration ranges of 0.5~1000.0 ng/mL for PTX and 0.25~500.0 ng/mL for 6α-OHP and 3'-OHP. The precision, accuracy, extraction recovery, and matrix effects were within acceptable limits. The present method was successfully applied to the study of the pharmacokinetics and distribution of PTX, 6α-OHP, and 3'-OHP in the tumors of post xenograft nude mice intravenously injected with PTX solution.

Keywords: 6α-hydroxypaclitaxel; HPLC–MS/MS; Paclitaxel; p-3′-hydroxypaclitaxel; pharmacokinetics and tissue distribution; solid-phase extraction.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms* / drug therapy
  • Paclitaxel* / chemistry
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods

Substances

  • Paclitaxel
  • 6-hydroxytaxol

Grants and funding

This work was supported by the Key Project of Jiangxi (Grant 20192ACB70012), the Key Project of Nanchang (2020-201-15) and Jiangxi University of Traditional Chinese Medicine 1050 Youth Talent Project, Nature Science Foundation for the Youth of Jiangxi (20181BAB205052 and 20192ACBL20005), Program from Bureau of Education, Jiangxi (GJJ60973), Key Laboratory of Cardiovascular and Cerebrovascular Diseases Prevention and Treatment of Ministry of Education (XN202026).