Development of a detection method for antisense oligonucleotides in mouse kidneys by matrix-assisted laser desorption/ionization imaging mass spectrometry

Rapid Communications in Mass Spectrometry : RCM
Hiroyuki YokoiHaruhiko Kamada

Abstract

Oligonucleotide therapeutics have recently gained much attention, but its pharmacokinetic evaluation methods are still not sufficient, and, in particular, more tools are needed to evaluate their tissue distribution and metabolites. We developed a matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS)-based method to evaluate the tissue distribution of oligonucleotide therapeutics. We used an antisense oligonucleotide containing locked nucleic acids (LNA-A). Various washing protocols were examined using mouse kidney homogenate sections. Next, we applied a two-step matrix preparation strategy. As a first step, 3-hydroxypicolinic acid (3-HPA) matrix containing citrate and amines was sprayed using an airbrush and subsequently 3-HPA matrix containing citrate only was sprayed using the ImagePrep. Finally, kidney sections prepared from LNA-A-dosed mice were treated with our optimized method and analyzed with MALDI-IMS. The selected washing method made it possible to detect LNA-A with MALDI-IMS and, furthermore, our developed matrix pretreatment method enhanced signal intensity approximately two-fold. MALDI-IMS revealed that LNA-A localized in a portion presumed to be the renal cortex. We also obtained inform...Continue Reading

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Citations

Dec 17, 2019·Rapid Communications in Mass Spectrometry : RCM·Yuko NakashimaMitsutoshi Setou
Feb 11, 2021·Analytical and Bioanalytical Chemistry·Jacob X M TruongPaul J Trim
Jun 2, 2021·Toxicologic Pathology·Fernando Romero-PalomoAnnamaria Braendli-Baiocco

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