Determination of S 12024 enantiomers in human plasma by liquid chromatography after chiral pre-column derivatization.
S 12024-2 is a new drug in phase II development that possesses cognitive enhancing properties. As its molecular structure has a chiral centre, a stereoselective method for the analysis of both enantiomers in human plasma has been developed. The method involves pre-column derivatization of the amine moiety with a homochiral reagent (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC), and chromatographic separation of the two diastereoisomers on an achiral reversed-phase cyanopropyl column, with fluorimetric detection (lambda ex = 260 nm; lambda em = 310 nm). A liquid-liquid extraction procedure with diethyl ether-dichloromethane (70:30, v/v) was used for sample preparation. This technique provides a linear response for both enantiomers over a concentration range of 10-500 ng ml-1 and the quantitation limit was set at 5 ng ml-1 in human plasma. Within-day and between-day precision and accuracy are within 9% limits for all concentrations assessed. This procedure was therefore used for determining both enantiomers in human plasma following oral administration of racemic S 12024-2 to elderly healthy subjects.
Boursier-Neyret
C
C
Bio-Pharmacie Servier, Orléans, France.
Baune
A
A
Klippert
P
P
Castagne
I
I
Sauveur
C
C
D000284:Administration, Oral; D000368:Aged; D000588:Amines / Q000737:chemistry; D002853:Chromatography, Liquid; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000097:blood*; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood*; D012044:Regression Analysis; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
D000588:Amines; D009025:Morpholines; D011804:Quinolines; C086272:S 12024