title: Solid phase microextraction and LC-MS/MS for the determination of paliperidone after stereoselective fungal biotransformation of risperidone.
abstract: The present work describes for the first time the use of SPME coupled to LC-MS/MS employing the polar organic mode in a stereoselective fungal biotransformation study to investigate the fungi ability to biotransform the drug risperidone into its chiral and active metabolite 9-hydroxyrisperidone (9-RispOH). 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 using a C18 fiber, 30 min of extraction time and 5 min of desorption time in the mobile phase. The method was completely validated and all parameters were in agreement with the literature recommendations. 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 stereoselectively biotransform risperidone into (+)- and (-)-9-RispOH enantiomers at different rates.
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Mariana Zuccherato
authors.initials: MZ
authors.lastname: Bocato
authors.forename: Rodrigo Almeida
authors.initials: RA
authors.lastname: Simões
authors.forename: Leandro Augusto
authors.initials: LA
authors.lastname: Calixto
authors.forename: Cristiane Masetto
authors.initials: CM
authors.lastname: de Gaitani
authors.forename: Mônica Tallarico
authors.initials: MT
authors.lastname: Pupo
authors.forename: Anderson Rodrigo Moraes
authors.initials: AR
authors.lastname: de Oliveira
mesh_terms: D001711:Biotransformation; D002853:Chromatography, Liquid; D003470:Culture Media; D020093:Cunninghamella / Q000378:metabolism*; D007555:Isoxazoles / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D018967:Risperidone / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D052617:Solid Phase Microextraction; D012997:Solvents; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D003470:Culture Media; D007555:Isoxazoles; D011743:Pyrimidines; D012997:Solvents; D018967:Risperidone; D000068882:Paliperidone Palmitate