Evaluation of microbiological and biomimetic models in stereoselective metabolism of risperidone by high-performance liquid chromatography / Avaliação de modelos microbiológicos e modelos biomiméticos no metabolismo estereosseletivo da risperidona por cromatografia líquida de alta eficiência

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

02/08/2012

RESUMO

Risperidone is an atypical antipsychotic drug. Its metabolism yields in two hydroxylated chiral metabolites, 7-hydroxyrisperidone (7-RispOH) and 9-hydroxyrisperidone (9-RispOH). The 9-RispOH metabolite presents the same pharmacologic activity of the parent drug risperidone. This led this drug to be marketed as drug under the generic name paliperidone. Studies have shown differences in the kinetic disposition of the 9-RispOH enantiomers with higher prevalence of the (+)-9-RispOH enantiomer in plasma. Thus, this work aimed to evaluate the ability of some species of fungi and Jacobsen catalysts in the enantioselective (bio)transformation of risperidone into its active chiral metabolite 9-RispOH. To accomplish that, it was developed a separation method to analyze risperidone and its metabolites by chiral high-performance liquid chromatography. This method was employed in enantioselective biotransformation studies and in asymmetric catalysis studies. The chromatographic separation was performed on a Chiralcel OJ-H column using methanol:ethanol (50:50, v/v) plus 0.2% triethylamine as the mobile phase at a flow rate of 0.8 mL min-1. The SPME process was performed by immersing directly a C18 probe fiber in the culture medium during 30 min. The analytes were desorbed from the fiber directly in the mobile phase during 5 min. The method validation and the biotransformation studies were performed by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The method was completely validated and all parameters were in agreement with the literature recommendations. The biotransformation studies were performed employing different species of fungi and only the Cunninghamella genus was able to biotransform risperidone into its active metabolite. The Cunninghamella echinulata fungus was able to biotransform risperidone into the active metabolite, (+)-9-RispOH, resulting in 100% of enantiomeric excess. The Cunninghamella elegans fungus was also able to biotransform stereoselectively risperidone into (+)- and ()-9-RispOH enantiomers at different rates. Preliminary studies of asymmetric catalysis were performed using high-performance liquid chromatography with UV-Vis detector (HPLC-UV). The aliquots were directly injected in the chromatography system. These studies showed that the reaction with 1:50:50 (catalyst:oxidant:substrate, in number of mols, in this sequence) presented an asymmetric catalysis of risperidone and that showed to be enantioselective to 7-RispOH (E1) metabolite.

ASSUNTO(S)

análise enantiosseletiva biotransformação biotransformation enantioselective analysis hplc risperidone spme spme

ACESSO AO ARTIGO

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