DETERMINATION OF FLUOXETINE ENANTIOMERS IN HUMAN SERUM AND URINE BY ISOCRATIC HPLC AND PRE-COLUMN FLUORESCENCE DERIVATIZATION WITH (R)-(+)-4-NITRO-7-(2-CHLOROFORMYLPYRROLIDIN-1-YL)-2,1,3-BENZOXADIAZOLE

摘要

Fluoxeline (FLX) is a highly selective serotonin reuptake inhibitor used as an antidepressant agent and administered as the racemate. In this study, we developed an isocralic HPLC method with fluorescence detection for the determination of FLX enanliomers ((R)-FLX and (S)-FLX) in human serum and urine, after pre-column derivalization with (R)-(+)-4-nilro-7-(2-chlorofonnyl-pyrrolidin-l-yl)-2,l,3-benzoxadiazole ((R)-(+)-NBD-Pro-COCl). After basic extraction of the samples into penlane, derivatizalion with (R)-(+)-NBD-Pro-COCl was conducted in borale buffer (pH 9.0) at 70degC for 5min. Prolriptyline was utilized as an internal standard. The regression equations for (R)-FLX hydrochloride and (S)-FLX hydrochhride in human serum showed good linearity in the range of 001-0.5 mug/mL with the detection limit of 0.005mug/mL and in the range of 0.025-0.5mug/mL with the detection limit of 0.008 mug/ mL, respectively. The corresponding values for human urine were 0.025-0.5 mug/ mL with the detection limit of 0.014 mug/ mL and 0.025-0.5 mug/mL with the detection limit of 0.010 mug/mL, respectively. The coefficients of variation were less than 11. 8%, and recovery was good. Our method using (R)-(+ )-NBD-Pro-COCl is useful for simultaneous determination of (R)-FLX and (S)-FLX in human serum and urine, and may be suitable for therapeutic drug monitoring.