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基于 CE-LIF 开发的体内脂质体阿霉素和游离阿霉素定量方法及其在药代动力学分析中的应用。

Liposomal doxorubicin and free doxorubicin in vivo quantitation method developed on CE-LIF and its application in pharmacokinetic analysis.

机构信息

State Key Laboratory Coal Resources and Safe Mining, China University of Mining and Technology-Beijing, Beijing, P. R. China.

School of Chemical and Environmental Engineering, China University of Mining and Technology-Beijing, Beijing, P. R. China.

出版信息

Electrophoresis. 2023 Sep;44(17-18):1361-1368. doi: 10.1002/elps.202300076. Epub 2023 Aug 14.

DOI:10.1002/elps.202300076
PMID:37578082
Abstract

As a novel drug delivery system, liposomes were used to improve pharmacokinetics/pharmacodynamics (PK/PD) characters, minimize toxicity, and enhance drug-target selectivity. However, heterogeneity of drug releasing process and liposome itself challenged traditional pharmaceutical analytical techniques, especially in vivo pharmacokinetic studies. In this study, a novel liposomal doxorubicin (L-DOX) pharmacokinetic analysis strategy was developed with capillary electrophoresis coupled with laser-induced fluorescence (CE-LIF) detector. The background electrolyte (BGE) system was composed of borate and sodium dodecyl sulfate (SDS), which was optimized to successfully achieve simultaneous online separation and quantitative analysis of free DOX and liposome-encapsulated DOX. The method was applied to the in vivo pharmacokinetic study of L-DOX in rats. The results showed that the concentration of total DOX (T-DOX) was gradually decreasing, while the concentration of L-DOX was relatively stable, with a concentration of 31.6 ± 4.8 µg/mL within 24 h. It was the first time to achieve liposomal drugs in vivo analysis with CE-LIF. CE-LIF was proved as potential rapidly real-time analytical methods for liposomal drugs in vivo occurrence monitoring.

摘要

作为一种新型的药物传递系统,脂质体被用于改善药代动力学/药效学(PK/PD)特性,降低毒性,并增强药物靶向选择性。然而,药物释放过程和脂质体本身的异质性挑战了传统的药物分析技术,特别是在体内药代动力学研究中。在本研究中,建立了一种新型的阿霉素脂质体(L-DOX)药代动力学分析策略,采用毛细管电泳结合激光诱导荧光(CE-LIF)检测器。背景电解质(BGE)系统由硼酸和十二烷基硫酸钠(SDS)组成,经过优化可成功实现游离 DOX 和脂质体包封的 DOX 的在线同时分离和定量分析。该方法应用于大鼠体内 L-DOX 的药代动力学研究。结果表明,总 DOX(T-DOX)的浓度逐渐降低,而 L-DOX 的浓度相对稳定,24 小时内浓度为 31.6±4.8 µg/mL。这是首次采用 CE-LIF 对体内脂质体药物进行分析。CE-LIF 被证明是一种用于体内监测脂质体药物发生的潜在快速实时分析方法。

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