Development and validation of an HPLC-MS/MS analytical method for quantitative analysis of TCBA-TPQ, a novel anticancer makaluvamine analog, and application in a pharmacokinetic study in rats

Chin J Nat Med. 2015 Jul;13(7):554-60. doi: 10.1016/S1875-5364(15)30051-0.

Abstract

We have recently designed and synthesized several novel iminoquinone anticancer agents that have entered preclinical development for the treatment of human cancers. Herein we developed and validated a quantitative HPLC-MS/MS analytical method for one of the lead novel anticancer makaluvamine analog, TCBA-TPQ, and conducted a pharmacokinetic study in laboratory rats. Our results indicated that the HPLC-MS/MS method was precise, accurate, and specific. Using this method, we carried out in vitro and in vivo evaluations of the pharmacological properties of TCBA-TPQ and plasma pharmacokinetics in rats. Our results provide a basis for future preclinical and clinical development of this promising anticancer marine analog.

Keywords: LC-MS/MS; Makaluvamine analogs; Pharmacokinetics; Rat plasma; TCBA-TPQ.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Animals
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid / methods*
  • Pyrroles / blood
  • Pyrroles / pharmacokinetics*
  • Quinolones / blood
  • Quinolones / pharmacokinetics*
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*

Substances

  • 7-(benzylamino)-1,3,4,8-tetrahydropyrrolo(4,3,2-de)quinolin-8(1H)-one
  • Antineoplastic Agents
  • Pyrroles
  • Quinolones