Assessment of the stereoselective fungal biotransformation of albendazole and its analysis by HPLC in polar organic mode.
A high-performance liquid chromatographic method using polar organic mode was developed to analyze albendazole (ABZ), albendazole sulfone (ABZSO(2)) and the chiral and active metabolite albendazole sulfoxide (ABZSOX, ricobendazole) that was further applied in stereoselective fungal biotransformation studies. The chromatographic separation was performed on a Chiralpak AS column using acetonitrile:ethanol (97:3, v/v) plus 0.2% triethylamine and 0.2% acetic acid as the mobile phase at a flow rate of 0.5 mL min(-1). The present study employed hollow fiber liquid-phase microextraction as sample preparation. The method showed to be linear over the concentration range of 25-5000 ng mL(-1) for each ABZSOX enantiomer, 200-10,000 ng mL(-1) for ABZ and 50-1000 ng mL(-1) for ABZSO(2) metabolite with correlation coefficient (r)>0.9934. The mean recoveries for ABZ, rac-ABZSOX and ABZSO(2) were, respectively, 9%, 33% and 20% with relative standard deviation below 10%. Within-day and between-day precision and accuracy assays for these analytes were studied at three concentration levels and were lower than 15%. This study opens the door regarding the possibility of using fungi in obtaining of the active metabolite ricobendazole. Nigrospora sphaerica (Sacc.) E. W. Mason (SS67), Pestalotiopsis foedans (VR8), Papulaspora immersa Hotson (SS13) and Mucor rouxii were able to stereoselectively metabolize ABZ into its chiral metabolite. Among them, the fungus Mucor rouxii was the most efficient in the production of (+)-ABZSOX.
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901, Ribeirão Preto, SP, Brazil.
Viviane Cangerana
VC
Hilário
Daniel Blascke
DB
Carrão
Thiago
T
Barth
Keyller Bastos
KB
Borges
Niege Araçari Jacometti Cardoso
NA
Furtado
Mônica Tallarico
MT
Pupo
Anderson Rodrigo Moraes
AR
de Oliveira
D015766:Albendazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D001203:Ascomycota / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation / Q000502:physiology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D013237:Stereoisomerism
C027187:albendazole sulfone; D015766:Albendazole; C027186:albendazole sulfoxide