Evaluation of Pharmacokinetics and Metabolism of Phosphorothioate Antisense Oligonucleotide G3139 in Rat by Capillary Electrophoresis with Laser-Induced Fluorescence

Eunmi Ban, Haejin Kwon, Eun Joo Song

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A sensitive and specific capillary electrophoresis with laser-induced fluorescence (CE-LIF) and a simple extraction process was developed to simultaneously detect G3139 and its metabolites as a model of antisense oligonucleotides (ASOs). This method has shown excellent linearity within the tested concentration range for G3139 and its metabolites, with a detection limit of 3.0 pM and a recovery of >84.2%. Based on our developed plasma extraction method, we have evaluated the pharmacokinetics and metabolites from rat plasma after intravenous administration of G3139 at 0.76 mg/kg. The results showed that G3139 and its metabolites were successfully simultaneously detected and analyzed through a single run using CE-LIF with baseline separation until the 30-h test sampling time point. The half-life of G3139 and its metabolites was observed at 31 and 68 h, respectively. This study may provide an effective analytical method for the pharmacokinetic and metabolite evaluation required to develop ASOs to treat a variety of diseases.

Original languageEnglish
Pages (from-to)316-320
Number of pages5
JournalNucleic Acid Therapeutics
Volume31
Issue number4
DOIs
StatePublished - Aug 2021

Bibliographical note

Funding Information:
This study was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (2020R1A4A4079494 and 2019R1A2C2004052). Eunmi Ban was supported by RP-Grant 2020 of Ewha Womans University.

Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.

Keywords

  • CE-LIF
  • G3139
  • metabolism
  • pharmacokinetics
  • phosphorothioate antisense oligonucleotides

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