Continuous enantiomer separation of the volatile inhalation anesthetic enflurane with a gas chromatographic simulated moving bed unit

Abstract The separation of the enantiomers of the racemic inhalation anesthetic enflurane was achieved by continuous gas phase simulated moving bed chromatography (GC–SMB). The productivity of the unit and the enantiomeric excess of the obtained streams were somehow low mainly because of the high operating temperature, i.e., T =50°C. As chiral stationary phase, an unpurified cyclodextrin derivative, consisting of various isomers and homologues and dissolved in an apolar polysiloxane matrix, was used. The competitive adsorption isotherms of ( R )-(−)-enflurane and ( S )-(+)-enflurane were determined by gas chromatographic measurements at increasing values of the pulse concentration in the range from linear to overload conditions. It has been shown that the adsorption behavior of the two enantiomers can be explained by considering enantioselective and non-enantioselective sites on the stationary phase. These results demonstrate the feasibility of the chiral resolution of enflurane by GC–SMB.

[1]  Massimo Morbidelli,et al.  Optimal operation of simulated moving bed units for nonlinear chromatographic separations , 1997 .

[2]  F. Charton,et al.  Comparison of the specific productivity of different chiral stationary phases used for simulated moving-bed chromatography , 1997 .

[3]  Massimo Morbidelli,et al.  Optimal operation of simulated moving-bed units for non-linear chromatographic separations: II. Bi-Langmuir isotherm , 1998 .

[4]  Paul Richert,et al.  Applications of simulated moving-bed chromatography to the separation of the enantiomers of chiral drugs , 1997 .

[5]  V. Kasche,et al.  Purification of monoclonal antibodies by simulated moving-bed chromatography. , 1997, Journal of chromatography. A.

[6]  Chromatographic resolution of enantiomers , 1998 .

[7]  Luís S. Pais,et al.  Separation of 1,1'-bi-2-naphthol enantiomers by continuous chromatography in simulated moving bed , 1997 .

[8]  J. Meinwald,et al.  Inhalational anesthetics stereochemistry: optical resolution of halothane, enflurane, and isoflurane , 1991, Science.

[9]  Masakazu Negawa,et al.  Optical resolution by simulated moving-bed adsorption technology , 1992 .

[10]  M. Juza,et al.  Analysis of charged cyclomalto-oligosaccharides (cyclodextrin) derivatives by ion-spray, matrix-assisted laser-desorption/ionization time-of-flight and fast-atom bombardment mass spectrometry, and by capillary electrophoresis. , 1996, Carbohydrate research.

[11]  Massimo Morbidelli,et al.  Robust design of countercurrent adsorption separation: 3. Nonstoichiometric systems , 1996 .

[12]  F. Antia,et al.  Enantioseparation of a chiral epoxide by simulated moving bed chromatography using Chiralcel-OD , 1995 .

[13]  M. Morbidelli,et al.  Performance of a Six-Port Simulated Moving-Bed Pilot Plant for Vapor-Phase Adsorption Separations , 1992 .

[14]  J. Meinwald,et al.  Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1. , 1995, Drug metabolism and disposition: the biological fate of chemicals.

[15]  Massimo Morbidelli,et al.  Vapor-Phase SMB Adsorptive Separation of Linear/Nonlinear Paraffins , 1996 .

[16]  E. Cavoy,et al.  Laboratory-developed simulated moving bed for chiral drug separations: Design of the system and separation of Tramadol enantiomers , 1997 .

[17]  Arvind Varma,et al.  Mathematical methods in chemical engineering , 1997 .

[18]  D. Staerk,et al.  Gas chromatographic separation of the enantiomers of volatile fluoroether anesthetics by derivatized cyclodextrins II. Preparative-scale separations for isoflurane , 1994 .

[19]  Massimo Morbidelli,et al.  Robust design of binary countercurrent adsorption separation processes , 1993 .

[20]  D. Staerk,et al.  Gas chromatographic separation of the enantiomers of volatile fluoroether anesthetics using derivatized cyclodextrin stationary phases. Part I , 1993 .

[21]  D. H. Everett.  Effect of gas imperfection on G.L.C. measurements : a refined method for determining activity coefficients and second virial coefficients , 1965 .

[22]  H. Nowotny,et al.  Separation of enantiomers on diluted permethylated β-cyclodextrin by high-resolution gas chromatography , 1988 .

[23]  V. Schurig,et al.  Preparative Enantiomer Separation of the Anesthetic Enflurane by Gas Inclusion Chromatography , 1993 .

[24]  Massimo Morbidelli,et al.  Robust design of countercurrent adsorption separation processes: 2. Multicomponent systems , 1994 .

[25]  Roger-Marc Nicoud,et al.  Complete design of a simulated moving bed , 1995 .

[26]  Michel Bailly,et al.  Preparative scale enantioseparation of a chiral epoxide: Comparison of liquid chromatography and simulated moving bed adsorption technology , 1993 .

[27]  A. Hierlemann,et al.  Chiral discrimination of inhalation anesthetics and methyl propionates by thickness shear mode resonators: new insights into the mechanisms of enantioselectivity by cyclodextrins. , 1997, Analytical chemistry.

[28]  Massimo Morbidelli,et al.  Experimental analysis of a chiral separation through simulated moving bed chromatography , 1999 .

[29]  D. Staerk,et al.  Gas chromatographic separation of the enantiomers of volatile fluoroether anesthetics by derivatized cyclodextrins. , 1994 .

[30]  M. Juza,et al.  Preparative enantiomer separation of the inhalation anesthetics enflurane, isoflurane and desflurane by gas chromatography on a derivatized gamma-cyclodextrin stationary phase. , 1997, Journal of chromatography. A.

[31]  G. Guiochon,et al.  Determination of the gas-liquid partition isotherms of the enantiomers of methyl 2-chloropropionate on trichloroacetyl pentyl β-cyclodextrin using the elution by characteristic points method , 1996 .

[32]  W. König,et al.  Cyclodextrins as chiral stationary phases in capillary gas chromatography. Part V: Octakis(3‐O‐butyryl‐2,6‐di‐O‐pentyl)‐γ‐cyclodextrin , 1989 .

[33]  V. Kasche,et al.  Continuous biospecific affinity purification of enzymes by simulated moving-bed chromatography theoretical description and experimental results , 1996 .

[34]  V. Schurig,et al.  Preparative enantiomer separation of enflurane and isoflurane by inclusion gas chromatography , 1994 .

[35]  S. Ergun.  Fluid flow through packed columns , 1952 .

[36]  M. Juza,et al.  Approach to the thermodynamics of enantionmer separation by gas chromatography Enantioselectivity between the chiral inhalation anesthetics enflurane, isoflurane and desflurane and a diluted γ-cyclodextrin derivative , 1997 .

[37]  David W. Guest,et al.  Evaluation of simulated moving bed chromatography for pharmaceutical process development , 1997 .

[38]  C. Ching,et al.  Preparative resolution of praziquantel enantiomers by simulated counter-current chromatography , 1993 .