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.
Bibliographical noteFunding 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.
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
- phosphorothioate antisense oligonucleotides