Issue 37, 2020

Rapid quantification of ruthenium(ii) polypyridyl anti-cancer drugs using a selective ligand dissociation LC-MS/MS method

Abstract

Research on Ru anti-cancer drugs is on the rise with many complexes in clinical trials. Inductively coupled plasma-mass spectrometry (ICP-MS) has been the standard technique for bioanalytical studies on Ru and Pt complexes in biological media. Tedious ICP-MS methods rely on detecting and quantifying the element while lacking important structural information of the original complexes. Despite being equally sensitive, more accessible, and highly selective to the target species, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not been validated for the analysis of Ru drugs. Using USFDA guidelines, we report here the optimization and validation of a facile LC-MS/MS method for the detection and quantification of three Ru(II) polypyridyl complexes in cells, plasma, and urine matrices. Importantly, a fast (10 min), single-step procedure was efficient for both extraction and sample purification, and analytes were rapidly eluted over a 3 min simple isocratic run. Specific parent ions were differentially fragmented by tandem MS, thus forming a unique and rational ligand dissociation chemistry that exhibits high selectivity to the target species with no measurable interferences or matrix effects. The developed LC-MS/MS method was advantageous vis-à-vis the prototypical ICP-MS based techniques both in vitro and in vivo, paving the way for its utilization in elaborate cellular uptake, pharmacokinetics, and pharmacodynamics studies.

Graphical abstract: Rapid quantification of ruthenium(ii) polypyridyl anti-cancer drugs using a selective ligand dissociation LC-MS/MS method

Supplementary files

Article information

Article type
Paper
Submitted
28 Jun 2020
Accepted
21 Aug 2020
First published
25 Aug 2020

Anal. Methods, 2020,12, 4517-4525

Rapid quantification of ruthenium(II) polypyridyl anti-cancer drugs using a selective ligand dissociation LC-MS/MS method

S. Mehanna, K. Bodman-Smith, C. F. Daher and R. S. Khnayzer, Anal. Methods, 2020, 12, 4517 DOI: 10.1039/D0AY01250E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements