The use of analytical methods for quality control of promising active pharmaceutical ingredients among derivatives of 4-oxoquinoline- 3-propanoic acids

V. O. Zubkov, N. I. Ruschak, M. M. Suleiman, A. O. Devyatkіna, I. S. Gritsenko

Abstract


Due to a global increase of microbial resistance to antimicrobial drugs the search for new antibiotics is vital for modern medicinal chemistry. 3-Quinolin-4-one propanoic acids have the molecular similarity with fluoroquinolone antibiotics and are prospective scaffold to create antimicrobial drugs. On the example of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid the analytical methods that can be used for quality control of promising active pharmaceutical ingredients (API) among derivatives of 3-(2-methyl-4 oxo-1,4-dihydroquinoline-3-yl) propanoic acids have been analyzed and tested. The necessity of their inclusion in the list of control methods of 13C NMR-spectroscopy, due to which the problem of the tautomeric forms of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid is uniquely solved, has been shown. Specific related substances, which are by-products of the synthesis of 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid – 1,2,3,4,9,10- hexahydroacridine-2,9-dione and 6a-hydroxy-5,6,6a, 8,9,14,15,16a, 17,18-decahydro-7,16-dioxa -5.14-diazaheptacene-9,18-dione, have been identified using liquid chromatography-mass spectrometry (LC-MS/MS). Recommendations for the use of UV- and IR-spectroscopy to develop quality control methods for 3-(2-methyl-4-oxo-1,4-dihydroquinoline-3-yl) propanoic acid have been proposed.


Keywords


antimicrobial resistance; quinolin-4-one; propanoic acid; standardization; quality control; NMR, LC-MS/MS

Full Text:

PDF

References


Державна фармакопея України / Державне підприємство «Науково-експертний фармакопейний центр». – 1-е вид. – Доп. 2. – Х.: РІРЕГ, 2008. – 617 с.

Державна фармакопея України / Державне підприємство «Науково експертний фармакопейний центр». – 1-е вид. – Доп. 4. – Х.: РІРЕГ, 2011. – 538 с.

2016 U.S. Pharmacopoeia-National Formulary [USP 39 NF 34]. Vol. 1. Rockville, Md: United States Pharmacopeial Convention, Inc, 2015.

Deak D., Outterson K., Powers J.H. et al. // Annals of Internal Medicine. – 2016. – Vol. 165, №5. – P. 363.

European Pharmacopoeia, 8-th ed. Directorate for the Quality of Medicines and Healthcare of the Council of Europe. – Strasbourg, France, 2013. – P. 1231.

Global Action Plan on Antimicrobial Resistance / WHO. – 2015.

Günther H. NMR-spectroscopy: basic principles, concepts and applications in chemistry. – John Wiley & Sons, 2013.

JChem 16.11.14.0, 2016, ChemAxon. (http://www.chemaxon.com).

Maggiora, Vogt M., Stumpfe D., et al. // J. of Med. Chem. – 2014. – Vol. 57, №8. – P. 3186-3204.

Premanandh J., Samara B.S., Mazen A.N. // Frontiers in Microbiol. – 2015. – Vol. 6. – P. 1536.

Santajit S., Indrawattana N. // BioMed Res. International. – 2016. – Vol. 2016. – P. 1-8.

Zubkov V.O., Osolodchenko T.P., Ruschak N.I. et al. // J. of Organic and Pharmac. Chem. – 2015. – Vol. 13, №4 (52). – P. 20-26.

Zubkov V.O., Rozhenko О.B., Ruschak N.I. et al. // J. of Organic and Pharmac. Chem. – 2011. – Vol. 14, №2. – P. 53-59.

Zubkov V.O., Tsapko T.O., Gritsenko I.S et al. // J. of Organic and Pharmac. Chem. – 2011. – Vol. 9, №4. – P. 38-41.


GOST Style Citations






DOI: https://doi.org/10.24959/93483

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)