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.

中文翻译：

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激光诱导荧光毛细管电泳评价硫代磷酸盐反义寡核苷酸 G3139 在大鼠体内的药代动力学和代谢

开发了一种灵敏且特异的激光诱导荧光 (CE-LIF) 毛细管电泳和简单的提取过程，以同时检测 G3139 及其代谢物作为反义寡核苷酸 (ASO) 的模型。该方法在 G3139 及其代谢物的测试浓度范围内表现出出色的线性，检测限为 3.0 pM，回收率 >84.2%。基于我们开发的血浆提取方法，我们评估了静脉注射 0.76 mg/kg G3139 后大鼠血浆中的药代动力学和代谢物。结果表明，在 30 小时测试采样时间点之前，使用 CE-LIF 与基线分离通过单次运行成功地同时检测和分析 G3139 及其代谢物。分别在 31 和 68 小时观察到 G3139 及其代谢物的半衰期。本研究可能为开发 ASO 治疗多种疾病所需的药代动力学和代谢物评估提供有效的分析方法。