Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin-Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus

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Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin-Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus. / Nemolochnova, Arina G; Rogachev, Artem D ; Salnikova, Olga P et al.

In: Pharmaceuticals, Vol. 15, No. 9, 1158, 18.09.2022.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{971d155223e34adb97d2cae15c4b356a,

title = "Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin-Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus",

abstract = "The stability of a new coumarin derivative, agent K-142, bearing α-pinene residue and possessing antiviral activity against respiratory syncytial virus (RSV) was studied in whole mice blood in vitro, and a method for its quantification in this matrix was developed and validated. The sample preparation method was precipitation of whole blood with a mixture of 0.2 M ZnSO4 with MeOH (2:8 v/v) containing 2-adamantylamine hydrochloride as an internal standard (IS). Analysis was carried out by HPLC-MS/MS using reversed phase chromatography and a triple quadrupole mass spectrometer 6500 QTRAP (SCIEX) in multiple reaction monitoring (MRM) mode. The transitions 351.2 → 217.1 Da and 152.2 → 93.1/107.2 Da were monitored for K-142 and the IS, respectively. The method was validated in terms of selectivity, calibration curve, LLOQ, accuracy and precision, stability, recovery and carry over. The developed method was used for a pharmacokinetics study of the compound after its oral administration to mice at a dose of 20 mg/kg.",

keywords = "antiviral activity, coumarin, LC-MS/MS, pharmacokinetics, RSV, terpene",

author = "Nemolochnova, {Arina G} and Rogachev, {Artem D} and Salnikova, {Olga P} and Khomenko, {Tatyana M} and Volcho, {Konstantin P} and Yarovaya, {Olga I} and Fatianova, {Alina V} and Pokrovsky, {Andrey G} and Salakhutdinov, {Nariman F}",

note = "Funding Information: This study was funded by the Russian Science Foundation (Moscow, Russia) grant No. 21-13-00026. Publisher Copyright: {\textcopyright} 2022 by the authors.",

year = "2022",

month = sep,

day = "18",

doi = "10.3390/ph15091158",

language = "English",

volume = "15",

journal = "Pharmaceuticals",

issn = "1424-8247",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "9",

}

RIS

TY - JOUR

T1 - Stability Study, Quantification Method and Pharmacokinetics Investigation of a Coumarin-Monoterpene Conjugate Possessing Antiviral Properties against Respiratory Syncytial Virus

AU - Nemolochnova, Arina G

AU - Rogachev, Artem D

AU - Salnikova, Olga P

AU - Khomenko, Tatyana M

AU - Volcho, Konstantin P

AU - Yarovaya, Olga I

AU - Fatianova, Alina V

AU - Pokrovsky, Andrey G

AU - Salakhutdinov, Nariman F

PY - 2022/9/18

Y1 - 2022/9/18

N2 - The stability of a new coumarin derivative, agent K-142, bearing α-pinene residue and possessing antiviral activity against respiratory syncytial virus (RSV) was studied in whole mice blood in vitro, and a method for its quantification in this matrix was developed and validated. The sample preparation method was precipitation of whole blood with a mixture of 0.2 M ZnSO4 with MeOH (2:8 v/v) containing 2-adamantylamine hydrochloride as an internal standard (IS). Analysis was carried out by HPLC-MS/MS using reversed phase chromatography and a triple quadrupole mass spectrometer 6500 QTRAP (SCIEX) in multiple reaction monitoring (MRM) mode. The transitions 351.2 → 217.1 Da and 152.2 → 93.1/107.2 Da were monitored for K-142 and the IS, respectively. The method was validated in terms of selectivity, calibration curve, LLOQ, accuracy and precision, stability, recovery and carry over. The developed method was used for a pharmacokinetics study of the compound after its oral administration to mice at a dose of 20 mg/kg.

AB - The stability of a new coumarin derivative, agent K-142, bearing α-pinene residue and possessing antiviral activity against respiratory syncytial virus (RSV) was studied in whole mice blood in vitro, and a method for its quantification in this matrix was developed and validated. The sample preparation method was precipitation of whole blood with a mixture of 0.2 M ZnSO4 with MeOH (2:8 v/v) containing 2-adamantylamine hydrochloride as an internal standard (IS). Analysis was carried out by HPLC-MS/MS using reversed phase chromatography and a triple quadrupole mass spectrometer 6500 QTRAP (SCIEX) in multiple reaction monitoring (MRM) mode. The transitions 351.2 → 217.1 Da and 152.2 → 93.1/107.2 Da were monitored for K-142 and the IS, respectively. The method was validated in terms of selectivity, calibration curve, LLOQ, accuracy and precision, stability, recovery and carry over. The developed method was used for a pharmacokinetics study of the compound after its oral administration to mice at a dose of 20 mg/kg.

KW - antiviral activity

KW - coumarin

KW - LC-MS/MS

KW - pharmacokinetics

KW - RSV

KW - terpene

UR - http://www.scopus.com/inward/record.url?scp=85138667180&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/c3c39bec-29c1-363c-98c9-1547d4b615e1/

U2 - 10.3390/ph15091158

DO - 10.3390/ph15091158

M3 - Article

C2 - 36145379

VL - 15

JO - Pharmaceuticals

JF - Pharmaceuticals

SN - 1424-8247

IS - 9

M1 - 1158

ER -

ID: 38005633