Resolutions of PZQ

Published by Ahamed on 1 May 2010 - 11:20pm
rac-PZQ 001.jpg1.66 MB

Analytical chromatography
There are many ways to analyse PZQ with enantioselective chromatography. The approach used in-house at Sydney.  We used ChiralcelOD-H column, Solvents: Hex:IPA:TEA 60:40:0.1, Flow Rate: 0.7 mL/min. The retention times were 12.362  & 14.932 mins. Sample HPLC trace is posted below.
Preparative chromatography
Paper detailing the preparative separation of PZQ enantiomers by Intervet:

Title: Taste, A New Incentive to Switch to (R)-Praziquantel in Schistosomiasis Treatment
Thorsten Meyer,1 Harald Sekljic,1 Stefan Fuchs,1 Heiko Bothe,1 Dieter Schollmeyer,2 and Christian Miculka1*

The preparative scale chromatography was performed on microcrystalline cellulose triacetate using methanol as the mobile phase, conditions under which the enantiomer having the negative optical rotation emerged first from the column [21]. After crystallisation from methanol/water, (−)-PZQ was obtained in enantiomeric excess >99%, as determined by HPLC (column used Chiralcel OD-H). No residual other enantiomer (+)-PZQ was detected in this sample. X-ray structural analysis, using Cu-Kα radiation, of a monoclinic crystal in hemi-hydrate form obtained from said fraction by crystallization from methanol/water unequivocally proved the R-configuration. Full paper is here.
(Edits by Mat Todd on this page)


ndt228's picture

Here is a 1993 reference to Simulated Moving Bed (SMB) chiral chromatographic separation of PZQ.  The stationary phase is microcrystalline cellulose triacetate (MCTA), and the stated production rate was 900 mg/hour of racemate separated.

MatTodd's picture

Nick - great find. We don't have the equipment to try this at Sydney. I will try to ask around if someone can do this for us, to provide some enantiopure material, but if there are any people out there willing to do this SMB separation of PZQ enantiomers, please post below!