Enantioselective fungal biotransformation of risperidone in liquid culture medium by capillary electrophoresis and hollow fiber liquid‐phase microextraction

Abstract

Knowing that microbial transformations of compounds play vital roles in the preparation of new derivatives with biological activities, risperidone and its chiral metabolites were determined by capillary electrophoresis and hollow fiber liquid-phase microextraction after a fungal biotransformation study in liquid culture medium. The analytes were extracted from 1 mL liquid culture medium into 1-octanol impregnated in the pores of the hollow fiber, and into an acid acceptor solution inside the polypropylene hollow fiber. The electrophoretic separations were carried out in 100 mmol/L sodium phosphate buffer pH 3.0 containing 2.0% w/v sulfated-α-CD and carboxymethyl-β-CD 0.5% w/v with a constant voltage of -10 kV. The method was linear over the concentration range of 100-5000 ng/mL for risperidone and 50-5000 ng/mL for each metabolite enantiomer. Within-day and between-day assay precisions and accuracies for all the analytes were studied at three concentration levels, and the values of relative standard deviation and relative error were lower than 15%. The developed method was applied in a pilot biotransformation study employing risperidone as the substrate and the filamentous fungus Mucor rouxii. This study showed that the filamentous fungus was able to metabolize risperidone enantioselectively into its chiral active metabolite, (-)-9-hydroxyrisperidone.

Combination of hollow‐fiber liquid‐phase microextraction and capillary electrophoresis for pioglitazone and its main metabolites determination in rat liver microsomal fraction

“…In addition, it should be strongly immobilized in the pores of the hollow fiber, and should provide appropriate extraction selectivity. Considering these characteristics, octanol was selected as organic solvent . In three‐phase systems, the use of strong acids as acceptor phase results in better recoveries for basic analytes, due to the efficient analyte protonation at low pH values.…”

Recent advances in electrodriven enantioseparations

“…The enantioselective biotransformation of albendazol to albendazolsulfoxide enantiomers by Penicillium crutosum was monitored by enantioselective CE . A similar methodological approach was applied in the assay of risperidone and 9‐hydroxyrisperidone as its chiral metabolite after incubation with the filamentous fungus Mucor rouxii .…”

Field‐amplified sample injection in capillary zone electrophoresis for the pharmacokinetic research of trace risperidone and its major metabolite 9‐hydroxyrisperidone in beagle dogs

“…To date, common separation methods have been reported for the determination of Risp and 9-OHRisp in various matrices based on HPLC determinations with UV [7][8][9][10][11][12], electrochemical detection [13], or mass spectrometric detection [12,[14][15][16][17], and capillary electrophoresis determinations with UV [18][19][20]. Among the methods mentioned above, some have drawbacks, such as long analysis time or inadequate sensitivity.…”

“…CE is rapidly developed as an alternative analytical tool with different separation mechanisms from those of HPLC because of its high efficiency, rapid separation, extremely low solvent consumption compared with HPLC, and small sample volume requirement [21,22]. To date, several groups have reported CE methods for the determination of Risp and 9-OHRisp [18][19][20]. However, these published CE assays are not suitable for the determination of biological samples of Risp and 9-OHRisp because of their low detection sensitivity and relatively long analysis time.…”

“…Danel et al [19] developed a chiral CE method for the simultaneous separation of Risp and the enantiomers of 9-OHRisp with LODs above 50 ng/mL and a runtime of 14 min. de Jesus et al [20] established another chiral CE method to study the fungal biotransformation of Risp with a lower quantitation limit (LLOQ) of >50 ng/mL and a runtime of 24 min. In fact, for multicomponent analysis, the typical analysis was 30 min.…”