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

N1 - Funding Information: This study was funded by the Russian Science Foundation (Moscow, Russia) grant No. 21-13-00026. Publisher Copyright: © 2022 by the authors.

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 -