Direct detection of the anti-cancer drug 9-phenylacridine in tissues by graphite rod laser desorption vacuum-ultraviolet post-ionization mass spectrometry

Rapid Commun Mass Spectrom. 2015 Jul 30;29(14):1328-34. doi: 10.1002/rcm.7226.

Abstract

Rationale: Traditionally, drug analysis in biological tissue by mass spectrometry has required complicated sample pre-treatment, which not only wasted time, but also had adverse effects on the results. In order to assist assessment of potential drugs rapidly and accurately, a direct analytical method for drug detection in tissues is needed. The development of such a method is described in this study.

Methods: An anti-cancer drug, 9-phenylacridine (ACPH), injected into the kidney of mice, was directly analysed from tissues placed on the surface of a graphite rod by near-infrared (1064 nm) laser desorption single photon ionization mass spectrometry (LD/SPI-MS).

Results: The LD/SPI-MS method was successfully validated by direct analysis of ACPH in kidney sections of mice, without any complicated and time-consuming sample pre-treatment. The sensitivity of detection was down to about 100 fmol per spot and the wide linear dynamic range allowed quantitative detection of ACPH in complex biological samples. A drug-time curve was acquired of ACPH in the kidney of mice after the drug had been injected into the caudal vein.

Conclusions: It was demonstrated that the anti-tumor drug ACPH could be directly and rapidly detected by LD/SPI-MS in biological tissues without any time-consuming pre-treatment procedure. This method could potentially be applied to the selective localization and analysis of small molecule drugs in tissues and to the study of the pharmacokinetics of new drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / administration & dosage
  • Acridines / pharmacokinetics*
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Graphite / chemistry
  • Kidney / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Vacuum

Substances

  • 9-phenylacridine
  • Acridines
  • Antineoplastic Agents
  • Graphite