The HPLC-MS determination of pharmacokinetic parameters of morpholinium 2-((4-(2-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate
Aim. To study pharmacokinetic parameters of the potential active pharmaceutical ingredient (API) morpholinium 2-((4-(2-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate in the blood plasma of rats when administered intraperitoneally.
Results and discussion. The HPLC-MS method of determination of morpholinium 2-((4-(2-methoxy)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate in the blood plasma of non-linear rats has been adopted to study of pharmacokinetic parameters of the compound. It has been proven that high levels of API extraction from the blood plasma when using methanol for protein precipitation were observed. The measurement of the concentration of the drug substance studied in the blood plasma at different time intervals after injection allowed us to plot the pharmacokinetic curve and calculate the pharmacokinetic parameters.
Experimental part. The Agilent 1260 Infinity liquid chromatography system consisted of a degasser, binary pump, autosampler, column thermostat, diode-matrix detector, single-quadrupole mass spectrometric detector (Agilent 6120). The pharmacokinetic study was performed in sexually mature white nonlinear rats of two sexes. The active pharmaceutical ingredient morpholinium 2-((4-(2-methoxy)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate, was administered in the isotonic solution intraperitoneally in the dose of 50 mg/kg.
Conclusions. The pharmacokinetic curve has been plotted, and the pharmacokinetic parameters of morpholinium 2-((4-(2-methoxy)-5-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)thio)acetate in the blood plasma when administered intraperitoneally have been calculated.
Full Text:PDF (Українська)
Samelyuk, Yu. G.; Kaplaushenko, A. G. Synthesis, physico-chemical and biological properties of 2-(5-(methoxyphenyl)-1,2,4-triazolo-3-thio)-acetic acid and their esters. Current issues in pharmacy and medicine: science and practice 2013, 2, 125 – 128.
Kaplaushenko, A. G. The Research of Creating a New Original Domestic Drug Based on 1,2,4-triazole. Scientific Journal of the Ministry of Health of Ukraine 2013, 2, 115 – 121.
Kaplaushenko, A. G. Synthesis, structure and biological activity of 4-mono-and 4,5-disubstituted 1,2,4-triazole-3-one derivatives. Doctoral Degree Thesis, Zaporizhzhya State Medical University, Zaporizhzhya, 2012.
Kaplaushenko, A. G. The study of pharmacokinetics of morpholinium 2-(5-(4-pyridyl)-4-(2-methoxyphenyl)-1,2,4-triazol-3-ylthio)acetate. Pharm. J. (Kiev, Ukr.) 2013, 6, 88 – 92.
Lim, C.-K.; Lord, G. Current Developments in LC-MS for Pharmaceutical Analysis. Biol. Pharm. Bull. 2002, 25 (5), 547 – 557. https://doi.org/10.1248/bpb.25.547.
Cuyckens, F. Mass spectrometry in drug metabolism and pharmacokinetics: Current trends and future perspectives. Rapid Commun. Mass Spectrom. 2019, 33 (S3), 90 – 95. https://doi.org/10.1002/rcm.8235.
Miroshnichenko, I. I.; Fedotov, Yu. A.; Gorshkova, E. V.; Ivaschenko, A. A. Chromatography mass spectrometry in pharmacokinetic investigations. Kachestvennaya klinicheskaya praktika 2008, 3, 29 – 36.
Varynskyi, B. O.; Kaplaushenko, A. G. HPLC and HPLC-MS methods used for drugs analysis in plasma and blood serum; Zaporizhzhya, 2019.
Silva, I. R.; Braga, A. V.; Gloria, M. B. d. A.; Machado, R. d. R.; César, I. C.; Oliveira, R. B. Preclinical pharmacokinetic study of a new thiazolyl hydrazone derivative with antifungal activity in mice plasma by LC-MS/MS. J. Chromatogr. B 2020, 1149, 122180. https://doi.org/10.1016/j.jchromb.2020.122180.
Logoyda, L.; Kovalenko, S.; Gaafar, M.; Abdel-Megied, A. M.; Elbarbry, F. A. A validated LC-MS/MS method for the quantification of amlodipine, bisoprolol, enalapril and enalaprilat. Application to pharmacokinetic study in healthy volunteers. Microchem. J. 2020, 155, 104700. https://doi.org/10.1016/j.microc.2020.104700.
Varynskyi, B.; Kaplaushenko, A. Metabolism study of morpholinium 2-((4-(2-methoxyphenyl)-5-(pyridin-4-yl)-4H-1,2,4-triazole-3-yl)thio)acetate. Current Issues in Pharmacy and Medical Sciences 2020, 33 (2), 72 – 75. https://doi.org/10.2478/cipms-2020-0014.
Pruglo, Ye. S. Synthesis and biological properties of 3-S-substituted 5-Alk-(Ar-,Het)-4(H)-R-1,2,4-triazole. Doctoral Degree Thesis, Zaporizhzhya State Medical University, Zaporizhzhya, 2019.
Shcherbyna, R. An investigation of the pharmacokinetics and potential metabolites of potassium 2-((4-amino-5-(morfolinometyl)-4H-1,2,4-triazol-3-yl)thio)acetate on rats. Ankara Univ. Eczacilik Fak. Derg. 2020, 44 (2), 233 – 241. https://doi.org/10.33483/jfpau.681611.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Abbreviated key title: J. Org. Pharm. Chem.
ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)