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

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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. / Охина, Алина Александровна; Rogachev, Artem D.; Yarovaya, Olga I. и др.

в: Journal of Pharmaceutical and Biomedical Analysis, Том 180, 113039, 20.02.2020.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

BibTeX

@article{7acb596d51694479acdca53706b15ed2,

title = "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",

abstract = "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 intra-day 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.",

keywords = "Anti-influenza, Blood-to-plasma distribution, Camphecene, LC-MS/MS, CELLS, IN-VITRO, EXTRACTION",

author = "Охина, {Алина Александровна} and Rogachev, {Artem D.} and Yarovaya, {Olga I.} and Khvostov, {Mikhail V.} and Tolstikova, {Tatyana G.} and Покровский, {Андрей Георгиевич} and Khazanov, {Veniamin A.} and Salakhutdinov, {Nariman F.}",

year = "2020",

month = feb,

day = "20",

doi = "10.1016/j.jpba.2019.113039",

language = "English",

volume = "180",

journal = "Journal of Pharmaceutical and Biomedical Analysis",

issn = "0731-7085",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - 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

AU - Охина, Алина Александровна

AU - Rogachev, Artem D.

AU - Yarovaya, Olga I.

AU - Khvostov, Mikhail V.

AU - Tolstikova, Tatyana G.

AU - Покровский, Андрей Георгиевич

AU - Khazanov, Veniamin A.

AU - Salakhutdinov, Nariman F.

PY - 2020/2/20

Y1 - 2020/2/20

N2 - 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 intra-day 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.

AB - 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 intra-day 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.

KW - Anti-influenza

KW - Blood-to-plasma distribution

KW - Camphecene

KW - LC-MS/MS

KW - CELLS

KW - IN-VITRO

KW - EXTRACTION

UR - http://www.scopus.com/inward/record.url?scp=85076516193&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2019.113039

DO - 10.1016/j.jpba.2019.113039

M3 - Article

C2 - 31865208

AN - SCOPUS:85076516193

VL - 180

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

M1 - 113039

ER -

ID: 22632960