Determination of alkaloid-inspired molecule vindeburnol in rabbit plasma by UPLC–HRMS and its application to pharmacokinetic studies and preliminary metabolite identification

Tsedilin, A.; Borets, L.; Riabova, O.; Kazakova, E.; Tafeenko, V.; Makarov, V.

Авторы: Tsedilin Andrey, Borets Lyudmila, Riabova Olga, Kazakova Elena, Tafeenko Victor, Makarov Vadim
Журнал: Journal of Pharmaceutical and Biomedical Analysis
Том: 239
Год издания: 2024
Издательство: Elsevier BV
Местоположение издательства: Netherlands
Номер статьи: 115917
DOI: 10.1016/j.jpba.2023.115917
Аннотация: The eburnamine-vincamine alkaloids exhibit a range of pharmacological activities. There is a limited understanding of the pharmacokinetics and pharmacodynamics of vindeburnol, a synthetic derivative of this chemical class of alkaloids. A fast and reliable UPLC-HRMS method was developed and validated to quantify vindeburnolin Soviet Chinchilla rabbit plasma from pharmacokinetics studies. An ultra-performance liquid chromatography system equipped with a Waters Acquity UPLC HSS T3 column was used for chromatographic separation by gradient elution with 0.1% (v/v) formic acid in water and acetonitrile. An Impact II QqTOF high-resolution massspectrometer equipped with an Apollo II electrospray ionization source was used for analysis in positive mode;the ions [M+H]+ m/z 269.1648 ± 0.003 and m/z 351.2067 ± 0.003 were monitored for vindeburnol and internalstandard (vinpocetine), respectively. Preliminary metabolite profiling was also performed, and thepharmacokinetics of the identified metabolites were evaluated. The mean retention times for vindeburnol and vinpocetine were 2.0 and 3.5 min. The UPLC–HRMS method was validated with accuracy and precision within the 15% acceptance limit (8.2% and 11.0%, respectively). The mean extraction recovery value of vindeburnolfrom rabbit plasma was 77%. Pharmacokinetic evaluation of vindeburnol revealed that the compound isdistributed rapidly with a short elimination half-life. Vindeburnol undergoes extensive first-pass metabolism andis metabolized into hydroxyvindeburnol and vindeburnol glucuronide.
Добавил в систему: Тафеенко Виктор Александрович

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Determination of alkaloid-inspired molecule vindeburnol in rabbit plasma by UPLC–HRMS and its application to pharmacokinetic studies and preliminary metabolite identificationстатья

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