Simple method for simultaneous quantification of two new derivatives of betulinic and ursolic acids with antimalarial activity by RP-HPLC-UV-CAD

Leonardo Trevisan Secretti; Andrea Pereira; Simone Cristina Baggio Gnoatto; Lívia Maronesi Bueno; Pâmela C. Lukasewics Ferreira; Pedro Eduardo Froehlich

doi:10.22456/2527-2616.108249

Authors

Leonardo Trevisan Secretti Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Andrea Pereira Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Simone Cristina Baggio Gnoatto Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Lívia Maronesi Bueno Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Pâmela C. Lukasewics Ferreira Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul
Pedro Eduardo Froehlich Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia - Universidade Federal do Rio Grande do Sul

DOI:

https://doi.org/10.22456/2527-2616.108249

Keywords:

Malaria, HPLC method, charged aerosol detector, drug candidates, mass balance

Abstract

Endemic in more than 90 countries and territories, malaria is the most widely, populational, and geographically, parasitic disease in the world. Plasmodium sp. resistance to available drugs is one of the biggest problems for malaria eradication. In this study, we develop a method for the simultaneous determination of two new derivatives of betulinic and ursolic acids with antimalarial activity designated 3-O-butanoylbetulinic and 3-O-butanoylursolic acids. An analytical method was developed by high-performance liquid chromatography coupled, in series, to ultraviolet (UV) and charged aerosol (CAD) detectors. The chromatographic system, operated isocratically by reversed-phase, consisted in a mobile phase composed of acetonitrile: water pH 3.0 adjusted with formic acid (85:15, v/v), flow rate of 1.2 mL/min and a PhenoSphere Next octadecylsilane column (250 mm x 4.6 mm, 5 μm particle size). Chromatograms were recorded simultaneously in UV and CAD, at a concentration of 50 µg mL-1, an injection volume of 20 μL at a controlled temperature of 50 °C. The method was found to be selective, linear (r > 0.99), precise (RSD < 2.0%), accurate, and robust for both analytes, and considered statistically validated, and can be applied to the identification and quantification of these new drug candidates.

Downloads

Download data is not yet available.

References

World Health Organization. World Malaria Report 2019. Available at: https://www.who.int/publications/i/item/worldmalaria-report-2019. Accessed August, 2020.

World Health Organization. World Malaria Report 2018. Available at: https://www.who.int/malaria/publications/worldmalaria-report-2018/en/. Accessed August, 2020.

Mehlotra RK, Mattera G, Bockarie MJ, Maguire JD, Baird JK, Sharma YD, et al. Discordant patterns of genetic variation at two chloroquine resistance loci in worldwide populations of the malaria parasite Plasmodium falciparum; Antimicrob. Agents Chemother. 2008; 52:2212-2222.

Woodrow CJ, Krishna S. Antimalarial drugs: recent advances in molecular determinants of resistance and their clinical significance. Cell. Mol. Life. Sci. 2006; 93:1586-1596.

Yogeeswari P, Sriram D. Betulinic acid and its derivatives: a review on their biological properties. Curr. Med. Chem. 2005; 12:657-666.

Bringmann G, Saeb W, Assi LA, François G, Naraya ASS, Peters K, et al. Betulinic acid: Isolation from Triphyophyllum peltatum and Ancistrocladus heyneanus, antimalarial activity, and crystal structure of the benzyl ester. Planta Med. 1997; 63: 255-257.

Silva GNS, Maria NRG, Schuck DC, Cruz LN, Moraes MS, Nakabashi M, et al. Two series of new semissynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action. Malar. J. 2013; 12: 89-96.

Fujioka T, Kashiwada Y, Kilkuskie RE, Cosentino LM, Ballas LM, Jiang JB, et al. Anti-AIDS agents, 11. Betulinic acid and platanic acid as anti-HIV principles from Syzigium claviflorum, and the anti-HIV activity of structurally related triterpenoids; J. Nat. Prod. 1994; 57:243-247.

Mayaux JF, Bousseau A, Pauwels R, Huet T, Hénin Y, Dereu N, et al. Triterpene derivatives that block entry of human immunodeficiency virus type 1 into cells; Proc. Natl. Acad. Sci. 1994; 91:3564-3568.

Kashiwada Y, Hashimoto F, Cosentino LM, Chen CH, Garrett PE, Lee KH. Betulinic acid and dihydrobetulinic acid derivatives as potent anti-HIV agents; J. Med. Chem. 1996; 39:1016-1017.

Mukherjee R, Kumar V, Srivastava SK, Agarwal SK, Burman AC. Betulinic acid derivatives as anticancer agents: structure activity relationship: Anticancer Agents Med. Chem. 2006; 6:271-279.

Schühly W, Heilmann J, Çalis I, Sticher O. New triterpenoids with antibacterial activity from Zizyphus joazeiro; Planta Med. 1999; 65:740-743.

Chandramu C, Manohar RD, Krupadanam DGL, Dashavantha RV. Isolation, characterization and biological activity of betulinic acid and ursolic acid from Vitex negundo L. Phytother. Res. 2003; 17:129- 134.

Carmona DBD, Erosa FE, Sosa KG, Pinell GR, Yapu DG, Bacab MJC, et al. Antiprotozoal activity of betulinic acid derivatives. Phytomed. 2010; 17:379- 382.

Liu J. Pharmacology of oleanolic acid and ursolic acid. J. Ethnopharmacol. 1995; 49:57-68.

Tokuda H, Origashi H, Koshimizu K, Ito Y. Inhibitory effects of ursolic and oleanolic acid on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. Cancer Lett. 1986; 33:279-285.

Ryu SY, Oak MH, Yoon SK, Cho DI, Yoo GS, Kim TS, Kim KM; Anti-allergic and anti-inflammatory triterpenes from the herb of Prunella vulgari. Planta Med. 2000; 66:358-360.

Suh N, Honda T, Finlay HJ, Barchowsky A, Williams C, Benoit NE, et al. Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse machophages; Cancer Res. 1998. 58:717-723.

César IC, Nogueira FHA, Pianetti GA; Simultaneous determination of artemether and limefantrine in fixed dose combination tables by HPLC with UV detection. J. Pharm. Biomed. Anal. 2008; 48:951-954.

Vehojec T, Obreza A. Review of operating principle and applications of the charged aerosol detector. J. Chromatogr. 2010; 1217:1549-1556.

Görög S. Drug safety, drug quality, drug analysis. J. Pharm. Biomed. Anal. 2008; 48:247-253.

International Conference on Harmonization (ICH) of Technical Requirements for the Registration of Pharmaceutical for Human Use. Validation of Analytical Procedures: Text and Methodology Q2(R1). Geneva, Switzerland, 2005.

Agência Nacional de Vigilância Sanitária (Anvisa). Resolução RDC nº 166 de 27 de julho de 2017. Dispõe sobre a validação de métodos analíticos e dá outras providências. Brasília, Brazil: Diário Oficial da União; 2017.

United States Pharmacopeia. USP 43-NF 38. Rockville: The United States Pharmacopoeial Convention, 2020.

Ma K, Wang H, Zhao M, Xing J. Purity determination and uncertainty evaluation of theophylline by mass balance method, high performance liquid chromatography and differential scanning calorimetry. Anal. Chim. Acta. 2009; 650:227-233.