Development and validation of an LC-MS/MS method for the quantitative analysis of the anti-influenza agent camphecene in rat plasma and its application to study the blood-to-plasma distribution of the agent

Development and validation of an LC-MS/MS method for the quantitative analysis of the anti-influenza agent camphecene in rat plasma and its application to study the blood-to-plasma distribution of the agent Научная публикация

Журнал

Journal of Pharmaceutical and Biomedical Analysis
ISSN: 0731-7085 , E-ISSN: 1873-264X

Вых. Данные

Год: 2020, Том: 180, Номер статьи : 113039, Страниц : DOI: 10.1016/j.jpba.2019.113039

Ключевые слова

Anti-influenza; Blood-to-plasma distribution; Camphecene; LC-MS/MS

Авторы

Okhina Alina A. ^1,2 , Rogachev Artem D. ^1,2 , Yarovaya Olga, I ^1,2 , Khvostov Mikhail, V ^1,2 , Tolstikova Tatyana G. ^1,2 , Pokrovsky Andrey G. ² , Khazanov Veniamin A. ³ , Salakhutdinov Nariman F. ^1,2

Организации

1	(Данные Web of science) NN Vorozhtsov Novosibirsk Inst Organ Chem, Acad Lavrentiev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Pirogov Str 2, Novosibirsk 630090, Russia
3	(Данные Web of science) Innovat Pharmacol Res LLC IPHAR, Elizarovikh Str 79-4, Tomsk 634021, Russia

A method of quantitative determination of camphecene, a new anti-influenza agent, in rat blood plasma based on LC-MS/MS was developed, validated and used to study the distribution of the agent between blood cells and blood plasma. The method was validated according to FDA and EMA recommendations in terms of selectivity, linearity, accuracy, precision, recovery, stability and carry-over. Plasma samples were precipitated with methanol followed by the addition of a methanolic solution of 2-adamantylamine hydrochloride (internal standard). HPLC analysis was performed on a reversed-phase column; the total time of analysis was 11 min, including column equilibration. MS/MS detection was performed on a 3200 QTRAP triple quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode. Transitions 196.4 -> 122.2/153.3 and 152.2 -> 93.1/107.2 were monitored for camphecene and the internal standard, respectively. The calibration curve was built in the concentration range of 10-5000 ng/ml. The intraday and inter-day accuracy and precision, carry-over and recovery were within the acceptable limits. It was found that, after spiking blood with camphecene and separating plasma, the concentration of the substance in the latter was close to its initial concentration in the blood. This property of the substance may be useful for clinical trials of the agent. It has also been established that the process of camphecene distribution (adsorption) between blood cells and blood plasma is reversible, and the amount of adsorbed substance is linearly dependent on its initial concentration in the blood for a wide range of concentrations, temperatures and hematocrit values. (C) 2019 Elsevier B.V. All rights reserved.

Okhina A.A. , Rogachev A.D. , Yarovaya O.I. , Khvostov M.V. , Tolstikova T.G. , Pokrovsky A.G. , Khazanov V.A. , Salakhutdinov N.F.
Development and validation of an LC-MS/MS method for the quantitative analysis of the anti-influenza agent camphecene in rat plasma and its application to study the blood-to-plasma distribution of the agent
Journal of Pharmaceutical and Biomedical Analysis. 2020. V.180. 113039 . DOI: 10.1016/j.jpba.2019.113039 WOS Scopus РИНЦ

Опубликована в печати:

1 февр. 2020 г.

Web of science	WOS:000514256500022
Scopus	2-s2.0-85076516193
РИНЦ	43220428
OpenAlex	W2995560834