Stereoselective degradation kinetics of tebuconazole in rabbits

Tebuconazole[(RS)-1-p-chlorophenyl-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol] is a potent triazole fungicide and consists of a pair of enantiomers. The enantioselective degradation kinetics of tebuconazole was investigated in rabbits by intravenous (iv) injection. The concentrations of (-)-(R)-tebuconazole and (+)-(S)-tebuconazole in plasma and tissues were determined by HPLC with a cellulose tris(3,5-dimethylphenylcarbamate)-based chiral stationary phase. Enantioselective analysis methods for this fungicide in plasma and tissues were developed and validated. Good linearities were obtained over the concentration range of 0.25-25 mg/l for both enantiomers. The degradation followed pseudo-first-order kinetics and the degradation of the (+)-(S)-tebuconazole was much faster than that of the (-)-(R)-tebuconazole in plasma after administration of racemic tebuconazole. This study also indicated that environmental assessment of enantiomeric degradation may be needed to fully evaluate risks of tebuconazole use.