The GC-SMB separation of the enantiomers of isoflurane

Abstract

The study of separation of the enantiomers of chiral anesthetic isoflurane on a cyclodextrin based stationary phase using a gas chromatography simulated moving bed process is reported. Experiments have been performed to investigate the effect of major operating parameters such as switch time, flow rates, and temperature. The study demonstrated that it is possible to separate the enantiomers to a high level of purity for use in clinical trials. It has also been found that the separation is very sensitive to disturbances as compared to the enflurane system that was studied previously

Contributions to the theory and practice of the chromatographic separation of enantiomers

“…stainless steel columns containing unpurified Lipodex E 7 in polysiloxane SE-54 coated on Chromosorb P (AW, DMCS, 80 -100 mesh) and operated at 35jC. 85,86 With the pure enantiomers of isoflurane and desflurane at hand, a …”

Gas Chromatographic Enantioseparation of Fluorinated Anesthetics: Single‐Column Performance and Scale‐up Estimation

“…A way to additionally increase the productivity is to lower the required purity. There are examples where the achieved purity of fluorinated anesthetics was not as high as in this work, e.g., , . For our system when the wanted purity was lowered to 90 %, the productivity of both isoflurane enantiomers reached the value of 4.97 g h −1 L ads −1 , while the recovery increased to 92 %.…”

“…For comparison, all publications with reported productivity values were selected. The checked processes were batch GC , and SMB separation . In Tab.…”

“…The first chiral separation of the mentioned anesthetics was performed on a microscale level using derivatives of α ‐ and γ ‐CD. The γ ‐CD derivative octakis(3‐ O ‐butyryl‐2,6‐di‐ O ‐pentyl)‐ γ ‐cyclodextrin developed by König et al provided further successful separations of racemic mixtures of the anesthetics in (semi)preparative single columns , , and by simulated moving bed (SMB) for isoflurane . The stationary phase was prepared by dissolving the selector ( γ ‐CD derivative) in polysiloxane SE‐54 and then coating it onto Chromosorb particles.…”

Salient Features of Enantioselective Gas Chromatography: The Enantiomeric Differentiation of Chiral Inhalation Anesthetics as a Representative Methodological Case in Point

“…In an attempt to scale-up the discontinuous preparative GC approach by a continuous enantioseparation of inhalation anesthetics, the simulated moving bed (SMB) technology has been employed in enantioselective GC, adapting the previous findings obtained in the batch-wise processes described above. Preliminary studies included enflurane [52,53] and isoflurane [54], which were enantioseparated on unpurified octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E) diluted in polysiloxane SE-54 and coated on Chromosorb P (AW, DMCS, 80-100 mesh). An optimized version of the enantioselective SMB unit later on consisted of eight 80 cm  15 mm (i.d.)…”