Comparison of accurate mass LC-MS and MRM LC-MS/MS for the quantification of a therapeutic small interfering RNA

Quantification of oligonucleotide strands from rat plasma has been assessed on two tandem quadrupole systems and a TOF-MS platform following a novel ion-exchange solid-phase extraction and ion-pair chromatographic separation. Limits of quantification are comparable across all three systems with excellent signal-to-noise and accuracy and precision data realised on the TOF-MS to 10 ng/mL. Despite the advances in tandem quadrupole performance in recent years this has not translated into a marked improvement in the detection limits on this instrument geometry. This may prove to be a feature of the tandem MS process for oligonucleotides and could limit the ability to realise lower detection limits on these types of instruments. (C) 2012 Elsevier B.V. All rights reserved.