Determination of YM992, a novel selective serotonin reuptake inhibitor, in rat and dog plasma by high-performance liquid chromatography with fluorescence detection.
A high-performance liquid chromatographic method with fluorescence detection was developed for the determination of (S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride (YM992) in plasma. Plasma samples were extracted with n-hexane under alkali condition. After the organic solvent was evaporated to dryness, the residue was treated with 4-fluoro-7-nitrobezofurazan (NBD-F) in borate buffer (pH 7.5) at room temperature for 20 min. The reaction was terminated with hydrochloric acid and the resultant solution was injected onto HPLC without further purification. No interfering peak was observed at the retention time of YM992 or the internal standard. The calibration curve was linear with the concentration of YM992 up to 200 ng/ml. The limit of quantitation was 1 ng/ml. The intra- and inter-day relative standard deviation was less than 5.6% and 4.1%, respectively, and the intra- and inter-day relative error ranged from -3.0% to 17.2% and 2.8% to 7.5%, respectively. Using the assay, the plasma concentration of YM992 could be determined up to 8 and 10 h after the oral administration of YM992 to rats and dogs, respectively.
Noguchi
K
K
Drug Metabolism Laboratories, Yamanouchi Pharmaceutical Co. Ltd, 1-8, Azusawa 1-Chome, Itabashi-ku, Tokyo 174-8511, Japan. noguchik@yamanouchi.co.jp
Watanabe
T
T
Higuchi
S
S
Chiba
K
K
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005456:Fluorescent Dyes; D008297:Male; D009025:Morpholines / Q000097:blood*; D051381:Rats; D011916:Rats, Inbred F344; D012044:Regression Analysis; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood*; D013045:Species Specificity; D013050:Spectrometry, Fluorescence
D009327:4-Chloro-7-nitrobenzofurazan; D005456:Fluorescent Dyes; D009025:Morpholines; D017367:Selective Serotonin Reuptake Inhibitors; C032930:7-fluoro-4-nitrobenzo-2-oxa-1,3-diazole; C105748:lubazodone hydrochloride