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

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.

Automated summary

A sensitive and specific capillary electrophoresis with laser-induced fluorescence (CE-LIF) method was developed for simultaneous detection of G3139 and its metabolites, with evaluation of pharmacokinetics in rat plasma. The method showed excellent linearity, detection limit, and recovery rate, allowing for effective analysis and providing valuable information for ASOs therapeutic research.