, Volume 82, Issue 1, pp 143–152 | Cite as

Characterization of Novel Polymer-Based Pyridine Stationary Phases for Supercritical Fluid Chromatography

  • Caroline WestEmail author
  • Elise Lemasson
  • Kanji Nagai
  • Tohru Shibata
  • Pilar Franco
  • Sophie Bertin
  • Philippe Hennig
  • Eric Lesellier
Part of the following topical collections:
  1. 50th Anniversary Commemorative Issue


2-Ethylpyridine-bonded silica is one of the most famous stationary phases employed in supercritical fluid chromatography, especially for the analysis of basic compounds and even without an additive in the mobile phase. In the present paper, we present the synthesis and characterization of three original stationary phases based on poly(vinylpyridine) polymers supported on silica. The position of nitrogen atom relative to the polymer chain was varied to be in the 2, 3, or 4 position. All these phases were prototypes, while the poly(4-vinylpyridine) phase was subsequently commercialized (DCPak P4VP from Daicel Corporation). The stationary phases obtained are characterized in supercritical fluid chromatography with carbon dioxide—methanol mobile phase, with a modified version of the solvation parameter model, to take account of ionic interactions. The three phases are also compared to a 2-ethylpyridine-bonded silica phase and a 2-picolylamine-bonded silica phase. It appears that the polymer-based pyridine phases are significantly more retentive than brush-type pyridine phases and adequately shield residual silanol groups to prevent unwanted interactions with basic compounds. The different selectivities and chromatographic performances are also evidenced with sample applications on pharmaceutical compounds, notably with a selection of 140 drug candidates.

Graphical abstract


Supercritical fluid chromatography (SFC) Linear solvation energy relationships (LSER) Quantitative structure–retention relationships (QSRR) Solvation parameter model Polymeric stationary phases 



Waters Corporation is warmly acknowledged for continuous support provided to Univ Orleans through the Centers of Innovation program. CW acknowledges the support of the Institut Universitaire de France (IUF), of which she is a Junior member.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interests.

Supplementary material

10337_2018_3598_MOESM1_ESM.pdf (197 kb)
Supplementary material 1 (PDF 197 KB)
10337_2018_3598_MOESM2_ESM.pdf (15 kb)
Supplementary material 2 (PDF 15 KB)


  1. 1.
    Lesellier E, West C (2015) The many faces of packed column supercritical fluid chromatography—a critical review. J Chromatogr A 1382:2–46. CrossRefGoogle Scholar
  2. 2.
    Nováková L, Grand-Guillaume Perrenoud A, Francois I et al (2014) Modern analytical supercritical fluid chromatography using columns packed with sub-2 µm particles: A tutorial. Anal Chim Acta 824:18–35. CrossRefGoogle Scholar
  3. 3.
    West C, Lesellier E (2008) Orthogonal screening system of columns for supercritical fluid chromatography. J Chromatogr A 1203:105–113. CrossRefGoogle Scholar
  4. 4.
    McClain R, Hyun MH, Li Y, Welch CJ (2013) Design, synthesis and evaluation of stationary phases for improved achiral supercritical fluid chromatography separations. J Chromatogr A 1302:163–173. CrossRefGoogle Scholar
  5. 5.
    Regalado EL, Makarov AA, McClain R et al (2015) Search for improved fluorinated stationary phases for separation of fluorine-containing pharmaceuticals from their desfluoro analogs. J Chromatogr A 1380:45–54. CrossRefGoogle Scholar
  6. 6.
    Grand-Guillaume Perrenoud AG-G, Farrell WP, Aurigemma CM et al (2014) Evaluation of stationary phases packed with superficially porous particles for the analysis of pharmaceutical compounds using supercritical fluid chromatography. J Chromatogr A 1360:275–287. CrossRefGoogle Scholar
  7. 7.
    Cazenave-Gassiot A, Boughtflower R, Caldwell J et al (2009) Effect of increasing concentration of ammonium acetate as an additive in supercritical fluid chromatography using CO2–methanol mobile phase. J Chromatogr A 1216:6441–6450. CrossRefGoogle Scholar
  8. 8.
    Grand-Guillaume Perrenoud A, Boccard J, Veuthey J-L, Guillarme D (2012) Analysis of basic compounds by supercritical fluid chromatography: attempts to improve peak shape and maintain mass spectrometry compatibility. J Chromatogr A 1262:205–213. CrossRefGoogle Scholar
  9. 9.
    Rao G, VN B, R DJ et al (2017) Supercritical fluid (CO2) chromatography for quantitative determination of selected cancer therapeutic drugs in the prescence of potential impurities in injection formulations. Anal Methods 9:3003–3018. CrossRefGoogle Scholar
  10. 10.
    Jin C, Guan J, Zhang D et al (2017) Supercritical fluid chromatography coupled with tandem mass spectrometry: a high-efficiency detection technique to quantify Taxane drugs in whole-blood samples. J Sep Sci 40:3914–3921. CrossRefGoogle Scholar
  11. 11.
    Crepier J, Le Masle A, Charon N et al (2018) Ultra-high performance supercritical fluid chromatography hyphenated to atmospheric pressure chemical ionization high resolution mass spectrometry for the characterization of fast pyrolysis bio-oils. J Chromatogr B 1086:38–46. CrossRefGoogle Scholar
  12. 12.
    Teubel J, Wüst B, Schipke CG et al (2018) Methods in endogenous steroid profiling—a comparison of gas chromatography mass spectrometry (GC–MS) with supercritical fluid chromatography tandem mass spectrometry (SFC–MS/MS). J Chromatogr A 1554:101–116. CrossRefGoogle Scholar
  13. 13.
    du Toit T, Bloem LM, Quanson JL et al (2017) Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone. J Steroid Biochem Mol Biol 166:54–67. CrossRefGoogle Scholar
  14. 14.
    Tu A, Ma Q, Bai H, Du Z (2017) A comparative study of triacylglycerol composition in Chinese human milk within different lactation stages and imported infant formula by SFC coupled with Q-TOF-MS. Food Chem 221:555–567. CrossRefGoogle Scholar
  15. 15.
    Cutrone JJ, Huang XS, Kozlowski ES et al (2017) Tiered analytics for purity assessment of macrocyclic peptides in drug discovery: analytical consideration and method development. J Pharm Biomed Anal 138:166–174. CrossRefGoogle Scholar
  16. 16.
    Scheuba J, Wronski V-K, Rollinger J, Grienke U (2017) Fast and green—co2 based extraction, isolation, and quantification of phenolic styrax constituents. Planta Med 83:1068–1075. CrossRefGoogle Scholar
  17. 17.
    Liu J, Sun S, Huang W, Zhang M (2017) Rapid determination of 15 antioxidants in polyolefins by ultra-performance convergence chromatography. Petrochem Technol 46:364–370Google Scholar
  18. 18.
    Laboureur L, Bonneau N, Champy P et al (2017) Structural characterisation of acetogenins from Annona muricata by supercritical fluid chromatography coupled to high-resolution tandem mass spectrometry: structural characterization of acetogenins by SFC-HRMS/MS. Phytochem Anal. Google Scholar
  19. 19.
    Wang M, Wang Y-H, Avula B et al (2017) Quantitative determination of cannabinoids in Cannabis and cannabis products using ultra-high-performance supercritical fluid chromatography and diode array/mass spectrometric detection. J Forensic Sci 62:602–611. CrossRefGoogle Scholar
  20. 20.
    Desfontaine V, Veuthey J-L, Guillarme D (2016) Evaluation of innovative stationary phase ligand chemistries and analytical conditions for the analysis of basic drugs by supercritical fluid chromatography. J Chromatogr A 1438:244–253. CrossRefGoogle Scholar
  21. 21.
    Laboureur L, Guérineau V, Auxilien S et al (2018) Profiling of modified nucleosides from ribonucleic acid digestion by supercritical fluid chromatography coupled to high resolution mass spectrometry. J Chromatogr A 1537:118–127. CrossRefGoogle Scholar
  22. 22.
    Shi X, Yang W, Qiu S et al (2018) Systematic profiling and comparison of the lipidomes from Panax ginseng, P. quinquefolius, and P. notoginseng by ultrahigh performance supercritical fluid chromatography/high-resolution mass spectrometry and ion mobility-derived collision cross section measurement. J Chromatogr A 1548:64–75. CrossRefGoogle Scholar
  23. 23.
    Hou J-J, Cao C-M, Xu Y et al (2018) Exploring lipid markers of the quality of coix seeds with different geographical origins using supercritical fluid chromatography mass spectrometry and chemometrics. Phytomedicine. Google Scholar
  24. 24.
    González-Mariño I, Thomas KV, Reid MJ (2018) Determination of cannabinoid and synthetic cannabinoid metabolites in wastewater by liquid-liquid extraction and ultra-high performance supercritical fluid chromatography-tandem mass spectrometry: cannabinoid derivatives in wastewater by UHPSFC-MS/MS. Drug Test Anal 10:222–228. CrossRefGoogle Scholar
  25. 25.
    Herpin L, Bichon E, Rambaud L et al (2018) Comparison between liquid chromatography and supercritical fluid chromatography coupled to mass spectrometry for beta-agonists screening in feeding stuff. J Chromatogr B 1086:130–137. CrossRefGoogle Scholar
  26. 26.
    Nagai K, Shibata T, Shinkura S, Ohnishi A (2018) Poly(butylene terephthalate) based novel achiral stationary phase investigated under supercritical fluid chromatography conditions. J Chromatogr A 1549:85–92. CrossRefGoogle Scholar
  27. 27.
    Nagai K, Shibata T, Shinkura S, Ohnishi A (2018) Poly(4-vinylpyridine) based novel stationary phase investigated under supercritical fluid chromatography conditions. J Chromatogr A. Google Scholar
  28. 28.
    Lemasson E, Bertin S, Hennig P et al (2015) Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part I: optimization of mobile phase composition. J Chromatogr A 1408:217–226. CrossRefGoogle Scholar
  29. 29.
    Nagai K, Shinkura S (2016) Stationary phase for supercritical fluid chromatography. WO2016/152996Google Scholar
  30. 30.
    West C, Melin J, Ansouri H, Mengue Metogo M (2017) Unravelling the effects of mobile phase additives in supercritical fluid chromatography. Part I: polarity and acidity of the mobile phase. J Chromatogr A 1492:136–143. CrossRefGoogle Scholar
  31. 31.
    Lemasson E, Bertin S, Hennig P et al (2015) Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part II. Selection of an orthogonal set of stationary phases. J Chromatogr A 1408:227–235. CrossRefGoogle Scholar
  32. 32.
    Lemasson E, Bertin S, Hennig P et al (2016) Comparison of ultra-high performance methods in liquid and supercritical fluid chromatography coupled to electrospray ionization—mass spectrometry for impurity profiling of drug candidates. J Chromatogr A 1472:117–128. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Univ Orleans, Institut de Chimie Organique et Analytique (ICOA), CNRS UMR 7311Orléans Cedex 2France
  2. 2.Daicel CorporationHimejiJapan
  3. 3.Chiral Technologies Europe, Parc d’Innovation, Bd. Gonthier d’AndernachIllkirch CedexFrance
  4. 4.Institut de Recherches ServierSuresnesFrance

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