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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Development and Validation of a Liquid Chromatographic Method for Aroylhydrazones at Hydrolytic Conditions

Author(s): Vania Maslarska, Stanislav Bozhanov, Stefka Ivanova and Violina T. Angelova*

Volume 17, Issue 4, 2021

Published on: 31 December, 2019

Page: [528 - 536] Pages: 9

DOI: 10.2174/1573412916666191231094046

Price: $65

Abstract

Background: The indole-containing aroylhydrazone derivatives 3a-c with potent antimycobacterial activity against a referent strain M. tuberculosis H37Rv and low cytotoxicity were evaluated for their stability via the precise and accurate HPLC analytical method in aqueous media of different pH (2.0, 7.0, 9.0 and 12.0).

Objective: The study describes the development and validation of a simple and reliable HPLC-UV procedure for the determination of aroylhydrazone derivatives and their hydrolytic stability. Additionally, to recognize if hydrolysis leads to generating undesired products, the degradation processes were identified.

Method: The separation was achieved with a LiChrosorb®RP-18 (250 x 4.6 mm) column, at ambient temperature with isocratic mode with mobile phase containing mixture of component A (acetonitrile) and component B (0.001M NaH2PO4, with 5 mM 1-heptane sulfonic acid sodium salt, adjusted to pH 3.0) in a ratio 60:40 (v/v). The flow rate was 1.0 ml/min and the eluent was monitored at 297 nm. The proposed method was validated as per ICH guidelines.

Result: The obtained results showed that the compounds were sensitive to hydrolytic decomposition in aqueous media, resulting in the splitting of the hydrazone bond. Rapid hydrolysis of substances was observed in the acid medium. The elevated temperature significantly accelerated the hydrolytic reaction. Relatively slow hydrolysis of 3a-c was observed in a neutral solution and aqueous solutions buffered to pH 9. The hydrolysis of 3a-c in neutral, alkaline and strong alkaline medium followed the pseudo- first-order reaction rate and showed a linear dependence of lnC versus time.

Conclusion: A validated high-performance liquid chromatographic assay for the determination of the hydrolytic stability of a series of aroylhydrazones was developed and optimized for the first time. The methods devised are successfully applicable to the development of pharmaceutical formulations.

Keywords: Aroylhydrazones, degradation products, HPLC, hydrolytic stability, method validation, chemotherapeutic agents.

Graphical Abstract
[1]
Kalia, J.; Raines, R.T. Hydrolytic stability of hydrazones and oximes. Angew. Chem. Int. Ed. Engl., 2008, 47(39), 7523-7526.
[http://dx.doi.org/10.1002/anie.200802651] [PMID: 18712739]
[2]
Elhakeem, M.A.; Taher, A.T.; Abuel-Maaty, S.M. Synthesis and anti-mycobacterial evaluation of some new isonicotinylhydrazide analogues. Bull. Fac. Pharm. Cairo Univ., 2015, 53, 45-52.
[http://dx.doi.org/10.1016/j.bfopcu.2014.11.001]
[3]
Kovaríková, P.; Mrkvicková, Z.; Klimeš, J. Investigation of the stability of aromatic hydrazones in plasma and related biological material. J. Pharm. Biomed. Anal., 2008, 47(2), 360-370.
[http://dx.doi.org/10.1016/j.jpba.2008.01.011] [PMID: 18294799]
[4]
Mandewale, M. C.; Patil, U. C.; Shedge, S. V.; Dappadwad, U. R.; Yamgar, R. S. A review on quinoline hydrazone derivatives as a new class of potent antitubercular and anticancer agents Beni-Suef University journal of basic and applied sciences 2017 6, 354-361.,
[5]
Alam, M.S.; Jebin, S.; Rahman, M.M.; Bari, M.L.; Lee, D-U. Biological and quantitative-SAR evaluations, and docking studies of (E)-N -benzylidenebenzohydrazide analogues as potential antibacterial agents. EXCLI J., 2016, 15, 350-361.
[PMID: 27540348]
[6]
Beteck, R.M.; Seldon, R.; Jordaan, A.; Warner, D.F.; Hoppe, H.C.; Laming, D.; Legoabe, L.J.; Khanye, S.D. Quinolone-isoniazid hybrids: synthesis and preliminary in vitro cytotoxicity and anti-tuberculosis evaluation. MedChemComm, 2019, 10(2), 326-331.
[http://dx.doi.org/10.1039/C8MD00480C] [PMID: 30881619]
[7]
Jansová, H.; Kubeš, J.; Reimerová, P.; Štěrbová-Kovaříková, P.; Roh, J.; Šimůnek, T. 2, 6-Dihydroxybenzaldehyde analogues of the iron chelator salicylaldehyde isonicotinoyl hydrazone: Increased hydrolytic stability and cytoprotective activity against oxidative stress. Chem. Res. Toxicol., 2018, 31(11), 1151-1163.
[http://dx.doi.org/10.1021/acs.chemrestox.8b00165] [PMID: 30395451]
[8]
Alzweiri, M.; Al-Marabeh, S.; Bardaweel, S.K.; Alfar, R.; Al-Hiari, Y.M. Stability determination for cyclized 2, 4-dinitrophenyl hydrazone derivative of glucose. J. Anal. Sci. Technol., 2017, 8, 9.
[http://dx.doi.org/10.1186/s40543-017-0117-x]
[9]
Vavříková, E.; Polanc, S.; Kočevar, M.; Horváti, K.; Bősze, S.; Stolaříková, J.; Vávrová, K.; Vinšová, J. New fluorine-containing hydrazones active against MDR-tuberculosis. Eur. J. Med. Chem., 2011, 46(10), 4937-4945.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.052] [PMID: 21855181]
[10]
Higgs, P.L.; Ruiz-Sanchez, A.J.; Dalmina, M.; Horrocks, B.R.; Leach, A.G.; Fulton, D.A. Enhancing the kinetics of hydrazone exchange processes: an experimental and computational study. Org. Biomol. Chem., 2019, 17(12), 3218-3224.
[http://dx.doi.org/10.1039/C9OB00058E] [PMID: 30840013]
[11]
Kölmel, D.K.; Kool, E.T. Oximes and hydrazones in bioconjugation: mechanism and catalysis. Chem. Rev., 2017, 117(15), 10358-10376.
[http://dx.doi.org/10.1021/acs.chemrev.7b00090] [PMID: 28640998]
[12]
Dirksen, A.; Dawson, P.E. Rapid oxime and hydrazone ligations with aromatic aldehydes for biomolecular labeling. Bioconjug. Chem., 2008, 19(12), 2543-2548.
[http://dx.doi.org/10.1021/bc800310p] [PMID: 19053314]
[13]
Schenk, G.H. Organic functional group analysis: theory and development, 2016.https://www.elsevier.com/books/organic-functional-group-analysis/schenk/978-0-08-103484-2
[14]
Nguyen, R.; Huc, I. Optimizing the reversibility of hydrazone formation for dynamic combinatorial chemistry. Chem. Commun. (Camb.), 2003, (8), 942-943.
[http://dx.doi.org/10.1039/b211645f] [PMID: 12744310]
[15]
Matson, J.B.; Stupp, S.I. Drug release from hydrazone-containing peptide amphiphiles. Chem. Commun. (Camb.), 2011, 47(28), 7962-7964.
[http://dx.doi.org/10.1039/c1cc12570b] [PMID: 21674107]
[16]
Brudno, Y.; Silva, E.A.; Kearney, C.J.; Lewin, S.A.; Miller, A.; Martinick, K.D.; Aizenberg, M.; Mooney, D.J. Refilling drug delivery depots through the blood. Proc. Natl. Acad. Sci. USA, 2014, 111(35), 12722-12727.
[http://dx.doi.org/10.1073/pnas.1413027111] [PMID: 25139997]
[17]
Cousins, G.R.; Furlan, R.L.; Ng, Y.F.; Redman, J.E.; Sanders, J.K. Identification and isolation of a receptor for N-methyl alkylammonium salts: Molecular amplification in a pseudo-peptide dynamic combinatorial library. Angew. Chem. Int. Ed., 2001, 40, 423-428.
[http://dx.doi.org/10.1002/1521-3773(20010119)40:2<423:AID-ANIE423>3.0.CO;2-6]
[18]
Cousins, G.L.; Sanders, J.M. Dynamic combinatorial libraries of pseudo-peptide hydrazone macrocycles. Chem. Commun. (Camb.), 1999, 1575-1576.
[http://dx.doi.org/10.1039/a904091i]
[19]
Simpson, M.G.; Pittelkow, M.; Watson, S.P.; Sanders, J.K. Dynamic combinatorial chemistry with hydrazones: libraries incorporating heterocyclic and steroidal motifs. Org. Biomol. Chem., 2010, 8(5), 1181-1187.
[http://dx.doi.org/10.1039/b917146k] [PMID: 20165811]
[20]
Ellis, S.; Kalinowski, D.S.; Leotta, L.; Huang, M.L.H.; Jelfs, P.; Sintchenko, V.; Richardson, D.R.; Triccas, J.A. Potent antimycobacterial activity of the pyridoxal isonicotinoyl hydrazone analog 2-pyridylcarboxaldehyde isonicotinoyl hydrazone: A lipophilic transport vehicle for isonicotinic acid hydrazide. Mol. Pharmacol., 2014, 85(2), 269-278.
[http://dx.doi.org/10.1124/mol.113.090357] [PMID: 24243647]
[21]
Angelova, V.T.; Pencheva, T.; Vassilev, N.; Simeonova, R.; Momekov, G.; Valcheva, V. New indole and indazole derivatives as potential antimycobacterial agents. Med. Chem. Res., 2019, 4, 485-497.
[http://dx.doi.org/10.1007/s00044-019-02293-w]
[22]
Commission, E.P. European Pharmacopoeia, 6th; EDQM: Strasbourg, 2008, p. 1097.
[23]
Guideline; I. H. T. In Tilte,, 2005.
[24]
Kalia, J. Bioconjugation: linkage stability and novel methods; ProQuest, 2008.,
[25]
Cordes, E.H.; Jencks, W.P. The mechanism of hydrolysis of Schiff bases derived from aliphatic amines. J. Am. Chem. Soc., 1963, 85, 2843-2848..
[http://dx.doi.org/10.1021/ja00901a037.]

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