Advertisement

Chromatographia

, Volume 82, Issue 1, pp 65–75 | Cite as

Recent Achievements and Future Challenges in Supercritical Fluid Chromatography for the Enantioselective Separation of Chiral Pharmaceuticals

  • Simona Felletti
  • Omar H. Ismail
  • Chiara De Luca
  • Valentina Costa
  • Francesco Gasparrini
  • Luisa Pasti
  • Nicola Marchetti
  • Alberto Cavazzini
  • Martina CataniEmail author
Review
Part of the following topical collections:
  1. 50th Anniversary Commemorative Issue

Abstract

During the last years, supercritical fluid chromatography (SFC) has attracted a continuously growing number of users. Thanks to the introduction of state-of-the-art equipment, this technique has allowed to run three-to-five times faster separations than in high-performance liquid chromatography (HPLC) on columns packed with particles of comparable dimension, at lower pressure drops and without loss of efficiency. Thanks to its high versatility, its high-throughput screening capability, and “green” character of the mobile phase, SFC has become particularly attractive for the separation of chiral drugs in pharmaceutical industries. In this review, we will consider the latest applications of SFC for the analysis of compounds of pharmaceutical interest and/or with biological activity essentially covering main achievements of the last 3 years. We also focus on some very recent, remarkable applications of SFC in ultrafast enantioseparations on chiral columns of the latest generation. Technical improvements needed on commercial equipment to increase the competitiveness of SFC towards highly efficient enantioseparations are discussed.

Keywords

Supercritical fluid chromatography (SFC) Chiral chromatography Enantioseparations Pharmaceuticals Ultrafast enantioseparations 

Notes

Compliance with ethical standards

Conflict of interest

The 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.
    Nikolai LN, McClure EL, Macleod SL, Wong CS (2006) Stereoisomer quantification of the beta-blocker drugs atenolol, metoprolol, and propranolol in wastewaters by chiral high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1131:103–109CrossRefGoogle Scholar
  2. 2.
    Sanganyado E, Lu Z, Fu Q, Schlenk D, Gan J (2017) Chiral pharmaceuticals: a review on their environmental occurrence and fate processes. Water Res 124:527–542CrossRefGoogle Scholar
  3. 3.
    Liu JT, Liu RH (2002) Enantiomeric composition of abused amine drugs: chromatographic methods of analysis and data interpretation. J Biochem Biophys Methods 54:115–146CrossRefGoogle Scholar
  4. 4.
    Nguyen LA, He H, Pham-Huy C (2006) Chiral drugs: an overview. J Biochem Biophys Methods 2:85–100Google Scholar
  5. 5.
    International conference on harmonization, IQ32A (R2): Impurities in new drug substances (2006)Google Scholar
  6. 6.
    Klesper E, Corwin AH, Turner DA (1962) High pressure gas chromatography above critical temperatures. J Org Chem 27:700–701CrossRefGoogle Scholar
  7. 7.
    Novotny M, Springston SR, Paeden PA, Fjeldsted JC, Lee ML (1981) Capillary supercritical fluid chromatography. Anal Chem 53:407A–411ACrossRefGoogle Scholar
  8. 8.
    Paeden PA, Fjeldsted JC, Springston SR, Lee ML, Novotny M (1982) Instrumental aspects of capillary supercritical fluid chromatography. Anal Chem 54:1090–1093CrossRefGoogle Scholar
  9. 9.
    Springston SR, Novotny M (1981) Kinetic optimization of capillary supercritical fluid chromatography using carbon dioxide as the mobile phase. Chromatographia 14:679–684CrossRefGoogle Scholar
  10. 10.
    Paeden PA, Lee ML (1983) Theoretical treatment of resolving power in open tubular column supercritical fluid chromatography. J Chromatogr 259:1–16CrossRefGoogle Scholar
  11. 11.
    Gere DR, Board R, McManigill D (1982) Supercritical fluid chromatography with small particle diameter packed columns. Anal Chem 54:736–740CrossRefGoogle Scholar
  12. 12.
    Crowther JB, Henion JD (1985) Supercritical fluid chromatography of polar drugs using small-particle packed columns with mass spectrometric detection. Anal Chem 57:2711–2716CrossRefGoogle Scholar
  13. 13.
    Schwarz HE (1987) LC-GC 5:14–22 Kindly provide article title for reference [13].Google Scholar
  14. 14.
    Desfontaine V, Guillarme D, Francotte E, Nováková L (2015) Supercritical fluid chromatography in pharmaceutical analysis. J Pharm Biomed Anal 113:56–71CrossRefGoogle Scholar
  15. 15.
    Lemasson E, Bertin S, West C (2016) Use and practice of achiral and chiral supercritical fluid chromatography in pharmaceutical analysis and purification. J Sep Sci 39:212–233CrossRefGoogle Scholar
  16. 16.
    Perrenoud AGG, Veuthey JL, Guillarme D (2012) Comparison of ultra-high performance supercritical fluid chromatography and ultra-high performance liquid chromatography for the analysis of pharmaceutical compounds. J Chromatogr A 1266:158–167CrossRefGoogle Scholar
  17. 17.
    Berger TA, Berger BK (2013) Separation of natural food pigments in saponified and un-saponified paprika oleoresin by ultra high performance supercritical fluid chromatography (UHPSFC). Chromatographia 76:591–601CrossRefGoogle Scholar
  18. 18.
    Poole, C.F. (ed.) (2017) Supercritical fluid chromatography, 1st Edition. Elsevier, New YorkGoogle Scholar
  19. 19.
    Kalíková K, Šlechtová T, Vozka J, Tesařová E (2014) Supercritical fluid chromatography as a tool for enantioselective separation; a review. Anal Chim Acta 821:1–33CrossRefGoogle Scholar
  20. 20.
    Lesellier E, West C (2015) The many faces of packed column supercritical fluid chromatography—a critical review. J Chromatogr A 1382:2–46CrossRefGoogle Scholar
  21. 21.
    Tarafder A (2016) Metamorphosis of supercritical fluid chromatography to sfc: an overview. TrAC 81:3–10Google Scholar
  22. 22.
    Vozka J, Kalíková K, Roussel C, Armstrong DW, Tesařová E (2013) An insight into the use of dimethylphenyl carbamate cyclofructan 7 chiral stationary phase in supercritical fluid chromatography: the basic comparison with HPLC. J Sep Sci. 81:1711–1719CrossRefGoogle Scholar
  23. 23.
    Mangelings D, Heyden YV (2008) Chiral separations in sub- and supercritical fluid chromatography. J Sep Sci 31:1252–1273CrossRefGoogle Scholar
  24. 24.
    Cavazzini A, Kaczmarski K, Szabelski P, Zhou D, Liu X, Guiochon G (2002) Modeling of the separation of the enantiomers of 1-phenyl-1-propanol on cellulose tribenzoate. J Chromatogr A 73:5705–5715Google Scholar
  25. 25.
    Li L (2016) Direct enantiomer determination of methorphan by HPLC-MS and SFC-MS. Forensic Chem 2:82–85CrossRefGoogle Scholar
  26. 26.
    Carnes S, O’Brien S, Szewczak A, Tremeau-Cayel L, Rowe WF, McCord B, Lurie IS (2017) Comparison of ultra high performance supercritical fluid chromatography, ultra high performance liquid chromatography, and gas chromatography for the separation of synthetic cathinones. J Sep Sci 40:3545–3556CrossRefGoogle Scholar
  27. 27.
    Hegstad S, Havnen H, Helland A, Falch BMH, Spigset O (2017) Enantiomeric separation and quantification of citalopram in serum by ultra-high performance supercritical fluid chromatography-tandem mass spectrometry. J Chromatogr B 1061–1062:103–109CrossRefGoogle Scholar
  28. 28.
    Nováková L, Douša M (2017) General screening and optimization strategy for fast chiral separations in modern supercritical fluid chromatography. Anal Chim Acta 950:199–210CrossRefGoogle Scholar
  29. 29.
    Khater S, Canault B, Azzimani T, Bonnet P, West C (2018) Thermodynamic enantioseparation behavior of phenylthiohydantoin-amino acid derivatives in supercritical fluid chromatography on polysaccharide chiral stationary phases. J Sep Sci 41:1450–1459CrossRefGoogle Scholar
  30. 30.
    Kawatzki K, Biba M, Regalado EL, Welch CJ (2016) Miser chiral supercritical fluid chromatography for high throughput analysis of enantiopurity. J. Chromatogr. A 1429:374–379CrossRefGoogle Scholar
  31. 31.
    Barhate CL, Lopez DA, Makarov AA, Bu X, Morris WJ, Lekhal A, Hartman R, Armstrong DW, Regalado EL (2018) Macrocyclic glycopeptide chiral selectors bonded to core-shell particles enables enantiopurity analysis of the entire verubecestat synthetic route. J Chromatogr A 1539:87–92CrossRefGoogle Scholar
  32. 32.
    Bu X, Regalado EL, Cuff J, Schafer W, Gong X (2016) Chiral analysis of poor uv absorbing pharmaceuticals by supercritical fluid chromatography-charged aerosol detection. J Supercrit Fluids 116:20–25CrossRefGoogle Scholar
  33. 33.
    West C, Konjaria ML, Shashviashvili N, Lemasson E, Bonnet P, Kakava R, Volonterio A, Chankvetadze B (2017) Enantioseparation of novel chiral sulfoxides on chlorinated polysaccharide stationary phases in supercritical fluid chromatography. J Chromatogr A 1499:174–182CrossRefGoogle Scholar
  34. 34.
    Khater S, Lozac’h MA, Adam I, Francotte E, West C (2016) Comparison of liquid and supercritical fluid chromatography mobile phases for enantioselective separations on polysaccharide stationary phases. J Chromatogr A 1467:463–472CrossRefGoogle Scholar
  35. 35.
    Kalíková K, Martínková M, Schmidt MG, Tesařová E (2018) Cellulose tris-(3,5-dimethylphenylcarbamate)-based chiral stationary phase for the enantioseparation of drugs in supercritical fluid chromatography: comparison with HPLC. J Sep Sci 41:1471–1478CrossRefGoogle Scholar
  36. 36.
    Hoguet V, Charton J, Hecquet PE, Lakhmi C, Lipka E (2018) Supercritical fluid chromatography versus high performance liquid chromatography for enantiomeric and diastereoisomeric separations on coated polysaccharides-based stationary phases: Application to dihydropyridone derivatives. J Chromatogr A 1549:39–50CrossRefGoogle Scholar
  37. 37.
    Vera CM, Shock D, Dennis GR, Farrell W, Shalliker RA (2017) Comparing the selectivity and chiral separation of D- and L-fluorenylmethyloxycarbonyl chloride protected amino acids in analytical high performance liquid chromatography and supercritical fluid chromatography; evaluating throughput, economic and environmental impact. J Chromatogr A 1493:10–18CrossRefGoogle Scholar
  38. 38.
    Hegstad S, Havnen H, Helland A, Spigset O, Frost J (2018) Enantiomeric separation and quantification of R/S-amphetamine in urine by ultra-high performance supercritical fluid chromatography tandem mass spectrometry. J Chromatogr B 1077–1078:7–12CrossRefGoogle Scholar
  39. 39.
    Jenkinson C, Taylor A, Storbeck KH, Hewison M (2018) Analysis of multiple vitamin d metabolites by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS). J Chromatogr B 1087–1088:43–48CrossRefGoogle Scholar
  40. 40.
    Khater S, West C (2015) Development and validation of a supercritical fluid chromatography method for the direct determination of enantiomeric purity of provitamin B5 in cosmetic formulations with mass spectrometric detection. J Pharm Biomed Anal 102:321–325CrossRefGoogle Scholar
  41. 41.
    Venkatramani CJ, Al-Sayah M, Li G, Goel M, Girotti J, Zang L, Wigman L, Yehl P, Chetwyn N (2016) Simultaneous achiral-chiral analysis of pharmaceutical compounds using two-dimensional reversed phase liquid chromatography-supercritical fluid chromatography. Talanta 148:548–555CrossRefGoogle Scholar
  42. 42.
    Goel M, Larson E, Venkatramani CJ, Al-Sayah M (2018) Optimization of a two-dimensional liquid chromatography-supercritical fluid chromatography-mass spectrometry (2D-LC-SFS-MS) system to assess in-vivo inter-conversion of chiral drug molecules. J Chromatogr B 1084:89–95CrossRefGoogle Scholar
  43. 43.
    Geryk R, Kalíková K, Schmid MG, Tesařova E (2016) Enantioselective separation of biologically active basic compounds in ultra-performance supercritical fluid chromatography. Anal Chim Acta 932:98–105CrossRefGoogle Scholar
  44. 44.
    Zhang L, Miao Y, Lin C (2018) Enantiomeric separation of six chiral pesticides that contain chiral sulfur/phosphorus atoms by supercritical fluid chromatography. J Sci Sep 41:1460–1470CrossRefGoogle Scholar
  45. 45.
    Tao Y, Zheng Z, Yu Y, Xu J, Liu X, Wu X, Dong F, Zheng Y (2018) Supercritical fluid chromatographytandem mass spectrometry-assisted methodology for rapid enantiomeric analysis of fenbuconazole and its chiral metabolites in fruits, vegetables, cereals, and soil. Food Chem 241:32–39CrossRefGoogle Scholar
  46. 46.
    Zhao L, Xie J, Guo F, Liu K (2018) Enantioseparation of napropamide by supercritical fluid chromatography: effects of the chromatographic conditions and separation mechanism. Chirality 30:661–669CrossRefGoogle Scholar
  47. 47.
    Cavazzini A, Marchetti N, Guzzinati R, Pierini M, Ciogli A, Kotoni D, D’Acquarica I, Villani C, Gasparrini F (2014) Enantioseparation by ultra-high-performance liquid chromatography. Trends Anal Chem 63:95–103CrossRefGoogle Scholar
  48. 48.
    Cancelliere G, Ciogli A, D’Acquarica I, Gasparrini F, Kocergin J, Misiti D, Pierini M, Ritchie H, Simone P, Villani C (2010) Transition from enantioselective high performance to ultra-high performance liquid chromatography: a case study of a brush-type chiral stationary phase based on sub-5-micron to sub-2-micron silica particles. J Chromatogr A 1217:990–999CrossRefGoogle Scholar
  49. 49.
    Catani M, Ismail OH, Felletti S, Gasparrini F, Pasti L, Costa V, Cavazzini A (2017) Pirkle-type chiral stationary phases for ultra-high performance ultra-fast enantioseparations. Am Pharmaceut Rev 20Google Scholar
  50. 50.
    Mazzoccanti G, Ismail OH, D’Acquarica I, Villani CM, Wilcox CM, Cavazzini A, Gasparrini F (2017) Cannabis through the looking glass: chemo- and enantio-selective separation of phytocannabinoids by enantioselective ultra high performance supercritical fluid chromatography. Chem Commun 53:12262–12265CrossRefGoogle Scholar
  51. 51.
    Sciascera L, Ismail O, Ciogli A, Kotoni D, Cavazzini A, Botta L, Szczerba T, Kocergin J, Villani C, Gasparrini F (2015) Expanding the potential of chiral chromatography for high-throughput screening of large compound libraries by means of sub-2 \(\upmu\)m Whelk-O1 stationary phase in supercritical fluid conditions. J Chromatogr A 1383:160–168CrossRefGoogle Scholar
  52. 52.
    Sánchez-Hernández L, Bernal JL, del Nozal MJ, Toribio L (2016) Chiral analysis of aromatic amino acids in food supplements usingsubcritical fluid chromatography and chirobiotic T2 column. J Supercrit Fluids 107:519–525CrossRefGoogle Scholar
  53. 53.
    Breitbach AS, Lim Y, Xu QL, Kürti YL, Armstrong DW, Breitbach ZS (2016) Enantiomeric separations of \(\alpha\)-aryl ketones with cyclofructan chiral stationary phases via high performance liquid chromatography and supercritical fluid chromatography. J Chromatogr A 1427:45–54CrossRefGoogle Scholar
  54. 54.
    Lajkó G, Ilisz I, Tóth G, Fülöp F, Lindner W, Péter A (2015) Application of Cinchona alkaloid-based zwitterionic chiral stationaryphases in supercritical fluid chromatography for theenantioseparation of n\(_{\alpha }\)-protected proteinogenic amino acids. J Chromatogr A 1415:134–145CrossRefGoogle Scholar
  55. 55.
    Wolrab D, Frühauf P, Gerner C, Kohout M, Lindner W (2017) Consequences of transition from liquid chromatography to supercritical fluid chromatography on the overall performance of a chiral zwitterionic ion-exchanger. J Chromatogr A 1517:165–175CrossRefGoogle Scholar
  56. 56.
    Rocchi S, Fanali C, Fanali S (2015) Use of a novel sub-2 \(\upmu\)m silica hydride vancomycin stationary phase in nano-liquid chromatography. ii. Separation of derivatized amino acid enantiomers. Chirality 27:767–772CrossRefGoogle Scholar
  57. 57.
    Barhate CL, Breitbach ZS, Costa Pinto E, Regalado EL, Welch CJ, Armstrong DW (2015) Ultrafast separation of fluorinated and desfluorinated pharmaceuticals using highly efficient and selective chiral selectors bonded to superficially porous particles. J Chromatogr A 1426:241–247CrossRefGoogle Scholar
  58. 58.
    Kotoni D, Ciogli A, D’Acquarica I, Kocergin J, Szczerba T, Ritchie H, Villani C, Gasparrini F (2012) Enantioselective ultra-high and high performance liquid chromatography: a comparative study of columns based on the Whelk-O1 selector. J Chromatogr A 1269:226–241CrossRefGoogle Scholar
  59. 59.
    Ismail OH, Ciogli A, Villani C, Martino MD, Pierini M, Cavazzini A, Bell DS, Gasparrini F (2016) Ultra-fast high-efficiency enantioseparations by means of a teicoplanin-based chiral stationary phase made on sub-2 \(\upmu\)m totally porous silica particles of narrow size distribution. J Chromatogr A 1427:55–68CrossRefGoogle Scholar
  60. 60.
    Ismail OH, Catani M, Pasti L, Cavazzini A, Ciogli A, Villani C, Kotoni D, Gasparrini F, Bell DS (2016) Experimental evidence of the kinetic performance achievable with columns packed with the new 1.9 \(\upmu\)m fully porous particles Titan C\(_{18}\). J Chromatogr A 1454:86–92CrossRefGoogle Scholar
  61. 61.
    Ismail OH, Pasti L, Ciogli A, Villani C, Kocergin J, Anderson S, Gasparrini F, Cavazzini A, Catani M (2016) Pirkle-type chiral stationary phase on coreshell and fully porousparticles: Are superficially porous particles always the better choice toward ultrafast high-performance enantioseparations? J Chromatogr A 1466:96–104CrossRefGoogle Scholar
  62. 62.
    Kharaishvili Q, Jibuti G, Farkas T, Chankvetadze B (2016) Further proof to the utility of polysaccharide-based chiral selectors in combination with superficially porous silica particles as effective chiral stationary phases for separation of enantiomers in high-performance liquid chromatography. J Chromatogr A 1467:163–168CrossRefGoogle Scholar
  63. 63.
    Catani M, Ismail OH, Gasparrini F, Antonelli M, Pasti L, Marchetti N, Felletti S, Cavazzini A (2017) Recent advancements and future directions of superficially porous chiral stationary phases for ultrafast high-performance enantioseparations. Analyst 142:555–566CrossRefGoogle Scholar
  64. 64.
    Ismail OH, Antonelli M, Ciogli A, Villani C, Cavazzini A, Catani M, Felletti S, Bell DS, Gasparrini F (2017) Future perspectives in high efficient and ultrafast chiral liquidchromatography through zwitterionic teicoplanin-based 2\(\upmu\)m superficially porous particles. J Chromatogr A 1520:91–102CrossRefGoogle Scholar
  65. 65.
    Catani M, Felletti S, Ismail OH, Gasparrini F, Pasti L, Marchetti N, Luca CD, Costa V, Cavazzini A (2018) New frontiers and cutting edge applications in ultra high performance liquid chromatography through latest generation superficially porous particles with particular emphasis to the field of chiral separations. Anal Bioanal Chem 410:2457–2465CrossRefGoogle Scholar
  66. 66.
    Patel DC, Breitbach ZS, Wahab MF, Barhate CL, Armstrong DW (2015) Gone in seconds: praxis, performance and peculiarities of ultrafast chiral liquid chromatography with superficially porous particles. Anal Chem 87:9137–9148CrossRefGoogle Scholar
  67. 67.
    Spudeit DA, Dolzan MD, Breitbach ZS, Barber WE, Micke GA, Armstrong DW (2014) Superficially porous particles vs. fully porous particles for bonded high performance liquid chromatographic chiral stationary phases: Isopropyl cyclofructan 6. J Chromatogr A 1363:89–95CrossRefGoogle Scholar
  68. 68.
    Regalado EL, Welch CJ (2015) Pushing the speed limit in enantioselective supercritical fluid chromatography. J Sep Sci 38:2826–2832CrossRefGoogle Scholar
  69. 69.
    Barhate CL, Wahab MF, Breitbach ZS, Bell DS, Armstrong DW (2015) High efficiency, narrow particle size distribution, sub-2 \(\upmu\)m based macrocyclic glycopeptide chiral stationary phases in HPLC and SFC. Anal Chim Acta 898:128–137CrossRefGoogle Scholar
  70. 70.
    Patel DC, Breitbach ZS, Yu J, Nguyen KA, Armstrong DW (2017) Quinine bonded to superficially porous particles for high-efficiency and ultrafast liquid and supercritical fluid chromatography. Anal Chim Acta 963:164–174CrossRefGoogle Scholar
  71. 71.
    Berger TA (2016) Kinetic performance of a 50 mm long 1.8 \(\upmu\)m chiral column in supercritical fluid chromatography. J Chromatogr A 1459:136–144CrossRefGoogle Scholar
  72. 72.
    Berger TA (2017) Preliminary kinetic evaluation of an immobilized polysaccharide sub-2 \(\upmu\)m column using a low dispersion supercritical fluid chromatograph. J Chromatogr A 1510:82–88CrossRefGoogle Scholar
  73. 73.
    Ismail OH, Losacco GL, Mazzoccanrti G, Ciogli A, Villani C, Catani M, Pasti L, Anderson S, Cavazzini A, Gasparrini F (2018) Unmatched kinetic performance in enantioselective supercritical fluid chromatography by combining latest generation Whelk-O1 chiral stationary phases with a low-dispersion in-house modified equipment. Anal Chem.  https://doi.org/10.1021/acs.analchem.8b01907
  74. 74.
    Barhate CL, Wahab MF, Tognarelli DJ, Berger TA, Armstrong DW (2016) Instrumental idiosyncrasies affecting the performance of ultrafast chiral and achiral sub/supercritical fluid chromatography. Anal Chem 88:8664–8672CrossRefGoogle Scholar
  75. 75.
    Speybrouck D, Lipka E (2016) Preparative supercritical fluid chromatography: a powerful tool for chiral separations. J Chromatogr A 1467:33–55CrossRefGoogle Scholar
  76. 76.
    Galea C, Mangelings D, Vander Heyden Y (2015) Method development for impurity profiling in SFC: the selection of a dissimilar set of stationary phases. J Pharm Biomed Anal 111:333–343CrossRefGoogle Scholar
  77. 77.
    Enmark M, Ȧsberg D, Leek H, Öhlén K, Klarqvist M, Samuelsson J, Fornstedt T (2015) Evaluation of scale-up from analytical to preparative supercritical fluid chromatography. J Chromatogr A 1425:280–286CrossRefGoogle Scholar
  78. 78.
    Landagaray E, Vaccher C, Yous S, Lipka E (2016) Design of experiments for enantiomeric separation in supercritical fluid chromatography. J Pharm Biomed Anal 120:297–305CrossRefGoogle Scholar
  79. 79.
    Sun M, Sandahl M, Turner C (2018) Comprehensive on-line two-dimensional liquid chromatography \(\times\) supercritical fluid chromatography with trapping column-assisted modulation for depolymerised lignin analysis. J Chromatogr A 1541:21–30CrossRefGoogle Scholar
  80. 80.
    Gargano AFG, Duffin M, Navarro P, Schoenmakers PJ (2016) Reducing dilution and analysis time in online comprehensive two-dimensional liquid chromatography by active modulation. Anal Chem 88:1785–1793CrossRefGoogle Scholar
  81. 81.
    Francois I, Pereira AD, Lynen F, Sandra P (2008) Construction of a new interface for comprehensive supercritical fluid chromatography x reversed phase liquid chromatography (SFC \(\times\) RPLC). J Sep Sci 1541:21–30Google Scholar
  82. 82.
    Pauw RD, Choikhet K, Desmet G, Broeckhoven K (2014) Occurrence of turbulent flow conditions in supercritical fluid chromatography. J Chromatogr A 1361:277–285CrossRefGoogle Scholar
  83. 83.
    Giddings JC (1965) Dynamics of Chromatography. Marcel Dekker, New YorkGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Chemistry and Pharmaceutical SciencesUniversity of FerraraFerraraItaly
  2. 2.Department of Drug Chemistry and Technology“Sapienza” University of RomeRomeItaly

Personalised recommendations