Preview

Pharmacokinetics and Pharmacodynamics

Advanced search

Quantification of a potential anticonvulsant drug GIZh-298 in rat plasma by liquid chromatography-mass spectrometry

https://doi.org/10.37489/2587-7836-2022-3-37-45

Abstract

GIZh-298 is a new derivative of 4-phenylpyrrolidone with anticonvulsant and nootropic effects. A selective and sensitive HPLC-MS technique for the quantitative determination of GIZh-298 in rat blood plasma has been developed and validated. The linearity of the technique was confirmed by a high correlation coefficient (>0.99). Recovery of GIZh-298 from blood plasma averaged 73.4 ±3.4 %. Accuracy during one working cycle and between cycles was < 4.01%, precision < 8.03 %. The study of the stability of GIZh-298 revealed that the target compound is stable in a biomatrix at room temperature (4 h), when it is in a thermostatically controlled autosampler (8 °C) during an analytical experiment, with prolonged storage at -50 ° C for 30 days, and also if it is subjected to several freeze-thaw cycles (3 cycle). The pharmacokinetics of GIZh-298 in rat blood plasma after a single intravenous injection at a dose of 60 mg/kg was studied.

About the Authors

P. O. Bochkov
FSBI «Zakusov Insti¬tute of Pharmacology»
Russian Federation

Bochkov Pavel O. PhD, Cand. Sci. (Biology), Senior Research Officer of laboratory pharmacokinetics 

SPIN code: 5576-8174

Moscow



O. Yu. Kravtsova
FSBI «Zakusov Insti¬tute of Pharmacology»
Russian Federation

Kravtsova Oxana Yu. PhD, Cand. Sci. (Biology), researcher scientist of pharmacokinetics laboratory 

SPIN code: 1733-2330

Moscow



G. B. Kolyvanov
FSBI «Zakusov Insti¬tute of Pharmacology»
Russian Federation

Kolyvanov Gennadiy B. Dr. Sci. in Biology, Leading researcher of the labo­ratory of pharmacokinetics

SPIN code: 2538-8639

Moscow



A. A. Litvin
FSBI «Zakusov Insti¬tute of Pharmacology»
Russian Federation

Litvin Alexander A. Dr. Sci. in Biology, Leading researcher of the labo­ratory of pharmacokinetics 

SPIN code: 6193-5770

Moscow



S. S. Boyko
FSBI «Zakusov Insti¬tute of Pharmacology»
Russian Federation

Boyko Svetlana S. PhD, Cand. Sci. (Biology), research officer of labo­ratory pharmacokinetics 

SPIN code: 4176-8921

Moscow



V. P. Zherdev
FSBI «Zakusov Insti¬tute of Pharmacology»
Russian Federation

Zherdev Vladimir P. Dr. Sci. (Med.), professor, Head of laboratory phar­macokinetics 

SPIN code: 2213-9592

Moscow



References

1. Durnev AD, Voronina TA, Litvinova SA, Nerobkova LN, Gajdukov IO, Gudasheva TA, Zhmurenko LA, Mokrov GV. Pat. RF № 2643091 31.01.2018 4-benzoylpyridine oxime derivatives having anticonvulsant activity as agents for treatment of epilepsy and paroxysmal states (In Russ).]. URL: https://patenton.ru/patent/RU2643091C2. Ссылка активна на 15.09.2022

2. Zhmurenko LA, Mokrov GV, Nerobkova LN, Litvinova SA, Gaydukov IO, Voronina TA, Gudasheva TA. Novel 4-benzoylpyridine oxime derivative GIZH-298 with ati-convuisant activity. Farmakokinetika i farmakodinamika = Pharmacokinetics and pharmacodynamics. 2017;(1):22—26. (In Russ).].

3. Gaydukov IO, Litvinova SA, Voronina TA, Nerobkova LN, Zhmurenko LA, Mokrov GV, Avakyan GG, Kutepova IS. 4-Benzoylpyridine oxime derivative (GIZH-298) versus valproic acid: the anticonvulsant potential effect in a model of epilepsy in rats with cobalt-induced lesions. Epilepsy and paroxysmal conditions. [Epilepsiya i paroksizmal’nye sostoyaniya]. 2017;9(2)57—66. (In Russ).]. DOI: 10.17749/2077-8333.2017.9.2.057-066

4. Izuchenie bioekvivalentnosti vosproizvedennykh lekarstvennykh sredstv. Rukovodstvo po ekspertize lekarstvennykh sredstv. Tom I. - M.: Grifi K; 2013. (In Russ).].

5. Rukovodstva po ekspertize lekarstvennykh sredstv Tom I, pravil provedeniya issledovanii bioekvivalentnosti lekarstvennykh preparatov v ramkakh Evraziiskogo ekonomicheskogo soyuza, Sovet Evraziiskoi ekonomicheskoi komissi, reshenie ot 3 noyabrya 2016 No. 85. (In Russ).].

6. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evolution and Research (CDER). Bioanalytical method validation. U.S. Government Printing Office: Washington, DC, 2018, 41 р.

7. ЕМА Guideline on bioanalytical method validation. European Medicines Agency. Committee for medicinal products for human use: London, 2011, 23 р.

8. Sergienko VI. Prikladnaya pharmakokinetika: osnovnye polozheniya I klinicheskoe primenenie / Ed by. VI Sergienko, R Jelliff, IB Bondareva // Moscow: Izdatelstvo RAMN. 2003. (In Russ).].


Review

For citations:


Bochkov P.O., Kravtsova O.Yu., Kolyvanov G.B., Litvin A.A., Boyko S.S., Zherdev V.P. Quantification of a potential anticonvulsant drug GIZh-298 in rat plasma by liquid chromatography-mass spectrometry. Pharmacokinetics and Pharmacodynamics. 2022;(3):37-45. (In Russ.) https://doi.org/10.37489/2587-7836-2022-3-37-45

Views: 445


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2587-7836 (Print)
ISSN 2686-8830 (Online)