title: 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.
authors: Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors: Liana I
authors: LI
authors: de Jesus
authors: Nayara C P
authors: NC
authors: Albuquerque
authors: Keyller B
authors: KB
authors: Borges
authors: Rodrigo A
authors: RA
authors: Simões
authors: Leandro A
authors: LA
authors: Calixto
authors: Niege A J C
authors: NA
authors: Furtado
authors: Cristiane M
authors: CM
authors: de Gaitani
authors: Mônica T
authors: MT
authors: Pupo
authors: Anderson R M
authors: AR
authors: de Oliveira
mesh_terms: D000704:Analysis of Variance; D001711:Biotransformation; D019075:Electrophoresis, Capillary / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007555:Isoxazoles / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D016014:Linear Models; D059627:Liquid Phase Microextraction / Q000379:methods*; D009089:Mucor / Q000378:metabolism*; D000068882:Paliperidone Palmitate; D010865:Pilot Projects; D011743:Pyrimidines / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D018967:Risperidone / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D007555:Isoxazoles; D011743:Pyrimidines; D018967:Risperidone; D000068882:Paliperidone Palmitate