Stereoselective determination of R-(+)- and S-(-)-remoxipride, a dopamine D2-receptor antagonist, in human plasma by chiral high-performance liquid chromatography.
A stereoselective high-performance liquid chromatographic (HPLC) method is described for the selective and sensitive quantitation in human plasma of R-(+)- and S-(-)-enantiomers of remoxipride. Remoxipride was extracted from basified plasma into hexane-methyl-tert.-butyl ether (20:80, v/v), washed with sodium hydroxide (1.0 M), then back-extracted into phosphoric acid (0.1 M). A structural analog of remoxipride was used as an internal standard. The sample extracts were chromatographed using a silica-based derivatized cellulose chiral column, Chiralcel OD-R, and a reversed-phase eluent containing 30-32% acetonitrile in 0.1 M potassium hexafluorophosphate. Ultraviolet (UV) absorbance detection was performed at 214 nm. Using 0.5-ml plasma aliquots, the method was validated in the concentration range 0.02-2.0 microg/ml and was applied in the investigation of systemic inversion of remoxipride enantiomers in man.
DePuy
M E
ME
Department of Drug Metabolism, Merck and Co. Inc., West Point, PA 19486, USA.
Demetriades
J L
JL
Musson
D G
DG
Rogers
J D
JD
D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D018492:Dopamine Antagonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D065127:Dopamine D2 Receptor Antagonists; D004355:Drug Stability; D006801:Humans; D008297:Male; D017330:Remoxipride / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013607:Tablets; D013810:Therapeutic Equivalency
D002214:Capsules; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D013607:Tablets; D017330:Remoxipride