Advertisement

Immobilized Cellulose-Based Chiralpak IC Chiral Stationary Phase for Enantioseparation of Eight Imidazole Antifungal Drugs in Normal-Phase, Polar Organic Phase and Reversed-Phase Conditions Using High-Performance Liquid Chromatography

  • Junyuan Zhang
  • Jiayi Sun
  • Yanru Liu
  • Jia YuEmail author
  • Xingjie GuoEmail author
Original
  • 18 Downloads

Abstract

Due to the remarkable enantioselective performances of polysaccharide derivatives, immobilized cellulose-based columns have high enantioseparation ability, which can be applied under various mobile phase conditions. In the present work, a cellulose-derived chiral stationary phase (CSP), namely Chiralpak IC was evaluated for enantioseparation of eight imidazole antifungal drugs (miconazole, econazole, isoconazole, sulconazole, butoconazole, fenticonazole, sertaconazole, and ketoconazole) in three mobile phase modes: normal-phase mode, polar organic mode and reversed-phase mode. The factors that affected the enantioseparation were investigated and optimized. Results indicated that the Chiralpak IC column possessed good enantioselectivity in three modes, with all analytes being successfully resolved. In addition, the mechanism of enantioseparation was preliminarily discussed based on the molecular structures and retention behavior of the enantiomers.

Graphical Abstract

Keywords

Chiral stationary phase Chiralpak IC column HPLC Enantiomeric separation Imidazole antifungal drug 

Notes

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Nguyen LA, He H, Pham-Huy C (2006) Chiral drugs: an overview. Int J Biomed Sci 2(2):85–100Google Scholar
  2. 2.
    Caner H, Groner E, Levy L, Agranat I (2004) Trends in the development of chiral drugs. Drug Discov Today 9(3):105–110Google Scholar
  3. 3.
    Brocks DR (2010) Drug disposition in three dimensions: an update on stereoselectivity in pharmacokinetics. Biopharm Drug Dispos 27(8):387–406Google Scholar
  4. 4.
    Schurig V (2016) The reciprocal principle of select and-selector-systems in supramolecular chromatography †. Molecules 21(11):1535Google Scholar
  5. 5.
    Han SM (2015) Direct enantiomeric separations by high performance liquid chromatography using cyclodextrins. Biomed Chromatogr 11(5):259–271Google Scholar
  6. 6.
    Riley CM, Rosanske TW, Riley SRR (2014) Specification of drug substances and products: development and validation of analytical methods. Elsevier, New YorkGoogle Scholar
  7. 7.
    Scriba GK (2016) Chiral recognition in separation science: an update. J Chromatogr A 1467:56–78Google Scholar
  8. 8.
    Ebinger K, Weller HN (2013) Comparison of chromatographic techniques for diastereomer separation of a diverse set of drug-like compounds. J Chromatogr A 1272(1):150–154Google Scholar
  9. 9.
    Toribio L, Bernal JL, Martín MT, Bernal J, Nozal MJ (2013) Effects of organic modifier and temperature on the enantiomeric separation of several azole drugs using supercritical fluid chromatography and the Chiralpak AD column. Biomed Chromatogr 28(1):152–158Google Scholar
  10. 10.
    Garzotti M, Hamdan M (2002) Supercritical fluid chromatography coupled to electrospray mass spectrometry: a powerful tool for the analysis of chiral mixtures. J Chromatogr B Anal Technol Biomed Life Sci 770(1):53–61Google Scholar
  11. 11.
    Gong ZS, Duan LP, Tang AN (2015) Amino-functionalized silica nanoparticles for improved enantiomeric separation in capillary electrophoresis using carboxymethyl-β-cyclodextrin (CM-β-CD) as a chiral selector. Microchim Acta 182(7–8):1297–1304Google Scholar
  12. 12.
    Knight J (2014) Specifications of drug substances and products: development and validation of analytical methods specifications of drug substances and products: development and validation of analytical methods. Org Process Res Dev 18(9):1154–1154Google Scholar
  13. 13.
    Zhang T, Nguyen D, Franco P (2008) Enantiomer resolution screening strategy using multiple immobilised polysaccharide-based chiral stationary phases. J Chromatogr A 1191(1):214–222Google Scholar
  14. 14.
    Francotte E, Tong Z (2016) Preparation and evaluation of immobilized 4-methylbenzoylcellulose stationary phases for enantioselective separations. J Chromatogr A 1467:214–220Google Scholar
  15. 15.
    Maier NM, Franco P, Lindner W (2001) Separation of enantiomers: needs, challenges, perspectives ☆. J Chromatogr A 906(1):3–33Google Scholar
  16. 16.
    Ghanem A, Wang C (2017) Enantioselective separation of racemates using CHIRALPAK IG amylose-based chiral stationary phase under normal standard, non-standard and reversed phase high performance liquid chromatography. J Chromatogr A 1532:89–97Google Scholar
  17. 17.
    Fanali S (2017) Nano-liquid chromatography applied to enantiomers separation. J Chromatogr A 1486:20–34Google Scholar
  18. 18.
    Bezhitashvili L, Bardavelidze A, Ordjonikidze T, Chankvetadze L, Chity M, Farkas T, Chankvetadze B (2017) Effect of pore-size optimization on the performance of polysaccharide-based superficially porous chiral stationary phases for the separation of enantiomers in high-performance liquid chromatography. J Chromatogr A 1482:32–38Google Scholar
  19. 19.
    Cirilli R, Ferretti R, Gallinella B, Zanitti L (2013) Retention behavior of proton pump inhibitors using immobilized polysaccharide-derived chiral stationary phases with organic-aqueous mobile phases. J Chromatogr A 1304(16):147–153Google Scholar
  20. 20.
    Lomsadze K, Jibuti G, Farkas T, Chankvetadze B (2012) Comparative high-performance liquid chromatography enantioseparations on polysaccharide based chiral stationary phases prepared by coating totally porous and core-shell silica particles. J Chromatogr A 1234(8):50–55Google Scholar
  21. 21.
    Shen J, Okamoto Y (2016) Efficient separation of enantiomers using stereoregular chiral polymers. Chem Rev 116(3):1094Google Scholar
  22. 22.
    Zhang X, Wang L, Dong S, Xia Z, Qi W, Liang Z, Shi Y (2016) Nanocellulose 3, 5-dimethylphenylcarbamate derivative coated chiral stationary phase: preparation and Enantioseparation performance. Chirality 28(5):376Google Scholar
  23. 23.
    Khater S, West C (2014) Insights into chiral recognition mechanisms in supercritical fluid chromatography V. Effect of the nature and proportion of alcohol mobile phase modifier with amylose and cellulose tris-(3,5-dimethylphenylcarbamate) stationary phases. J Chromatogr A 1373:197–210Google Scholar
  24. 24.
    Chankvetadze B, Yamamoto C, Okamoto Y (2001) Enantioseparation of selected chiral sulfoxides using polysaccharide-type chiral stationary phases and polar organic, polar aqueous–organic and normal-phase eluents. J Chromatogr A 922(1):127–137Google Scholar
  25. 25.
    Cirilli R, Ferretti R, Gallinella B, Bilia AR, Vincieri FF, La Torre F (2015) Enantioseparation of kavain on Chiralpak IA under normal-phase, polar organic and reversed-phase conditions. J Sep Sci 31(12):2206–2210Google Scholar
  26. 26.
    Matarashvili I, Shvangiradze I, Chankvetadze L, Sidamonidze S, Takaishvili N, Farkas T, Chankvetadze B (2015) High-performance liquid chromatographic separations of stereoisomers of chiral basic agrochemicals with polysaccharide-based chiral columns and polar organic mobile phases. J Sep Sci 38(24):4173–4179.  https://doi.org/10.1002/jssc.201500919 Google Scholar
  27. 27.
    Baddley JW, Moser SA (2004) Emerging fungal resistance. Clin Lab Med 24(3):721–735Google Scholar
  28. 28.
    Alffenaar JWC, Wessels AMA, Hateren KV, Greijdanus B, Kosterink JGW, Uges DRA (2010) Method for therapeutic drug monitoring of azole antifungal drugs in human serum using LC/MS/MS. J Chromatogr B Anal Technol Biomed Life Sci 878(1):39–44Google Scholar
  29. 29.
    Pyrgaki C, Bannister SJ, Gera L, Gerber JG, Gal J (2011) Stereoselective determination of the epimer mixtures of itraconazole in human blood plasma using HPLC and fluorescence detection. Chirality 23(7):495–503Google Scholar
  30. 30.
    Feng Z, Zou Q, Tan X, Che W, Zhang Z (2011) Determination of fenticonazole enantiomers by LC-ESI-MS/MS and its application to pharmacokinetic studies in female rats. Arzneimittelforschung 61(10):587–593Google Scholar
  31. 31.
    Chankvetadze B, Kartozia I, Yamamoto C, Okamoto Y (2002) Comparative enantioseparation of selected chiral drugs on four different polysaccharide-type chiral stationary phases using polar organic mobile phases. J Pharm Biomed Anal 27(3):467–478Google Scholar
  32. 32.
    Mskhiladze A, Karchkhadze M, Dadianidze A, Fanali S, Farkas T, Chankvetadze B (2013) Enantioseparation of chiral antimycotic drugs by HPLC with polysaccharide-based chiral columns and polar organic mobile phases with emphasis on enantiomer elution order. Chromatographia 76(21–22):1449–1458Google Scholar
  33. 33.
    Thienpont A, Gal J, Aeschlimann C, Félix G (1999) Studies on stereoselective separations of the “azole’’ antifungal drugs ketoconazole and itraconazole using HPLC and SFC on silica-based polysaccharides. Analusis 27(8):713–718Google Scholar
  34. 34.
    Aboul-Enein HY, Ali I (2002) Comparative study of the enantiomeric resolution of chiral antifungal drugs econazole, miconazole and sulconazole by HPLC on various cellulose chiral columns in normal phase mode. J Pharm Biomed Anal 27(3):441–446Google Scholar
  35. 35.
    Zhang T, Nguyen D, Franco P (2010) Reversed-phase screening strategies for liquid chromatography on polysaccharide-derived chiral stationary phases. J Chromatogr A 1217(7):1048–1055Google Scholar
  36. 36.
    Zhu B, Deng M, Yao Y, Yu J, Li Q (2018) Comparative studies of immobilized chiral stationary phases based on polysaccharide derivatives for enantiomeric separation of 15 azole compounds. Electrophoresis.  https://doi.org/10.1002/elps.201800180 Google Scholar
  37. 37.
    Mosiashvili L, Chankvetadze L, Farkas T, Chankvetadze B (2013) On the effect of basic and acidic additives on the separation of the enantiomers of some basic drugs with polysaccharide-based chiral selectors and polar organic mobile phases. J Chromatogr A 1317(19):167–174Google Scholar
  38. 38.
    Gogaladze K, Chankvetadze L, Tsintsadze M, Farkas T, Chankvetadze B (2015) Effect of basic and acidic additives on the separation of some basic drug enantiomers on polysaccharide-based chiral columns with acetonitrile as mobile phase. Chirality 27(3):228Google Scholar
  39. 39.
    Matarashvili I, Ghughunishvili D, Chankvetadze L, Takaishvili N, Khatiashvili T, Tsintsadze M, Farkas T, Chankvetadze B (2016) Separation of enantiomers of chiral weak acids with polysaccharide-based chiral columns and aqueous-organic mobile phases in high-performance liquid chromatography: typical reversed-phase behavior? J Chromatogr A 1483:86–92Google Scholar
  40. 40.
    Berthod A (2006) Chiral recognition mechanisms. Anal Chem 78(7):2093–2099Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.School of PharmacyShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China

Personalised recommendations