Investigation of the stereoselective metabolism of praziquantel after incubation with rat liver microsomes by capillary electrophoresis and liquid chromatography-mass spectrometry.
Two different separation methods for the antischistosomal drug praziquantel and its metabolites by capillary electrophoresis are described. Achiral separation was obtained by micellar electrokinetic capillary chromatography using sodium dodecyl sulfate as micelle-forming surfactant. On the other hand, the negatively charged sulfobutylether-beta-cyclodextrin as a chiral selector enabled the separation of the drug and its metabolites as well as their enantioseparation. Based on this separation, the enantioselectivity of the metabolism of praziquantel was studied by incubation of the drug with rat liver microsomes. Whereas trans- and cis-4-hydroxypraziquantel were mainly formed from the R-(-)-enantiomer, another, different monohydroxylated metabolite was only formed from the S-(+)-enantiomer. Information about the structure of these metabolites was obtained, using LC-MS.
Lerch
C
C
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
Blaschke
G
G
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods*; D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D008823:Micelles; D008862:Microsomes, Liver / Q000378:metabolism*; D011223:Praziquantel / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins
D000980:Antiplatyhelmintic Agents; D003505:Cyclodextrins; D008823:Micelles; D013501:Surface-Active Agents; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; C067550:4-hydroxypraziquantel; D011223:Praziquantel