Enantiospecific determination of PNU-83894 and its major metabolite, PNU-83892, in plasma, and its application to the characterization of the enantioselective pharmacokinetics of PNU-83894 in the dog.
A chiral method for the simultaneous analysis of the (+)- and (-)-enantiomers of PNU-83894 and its metabolite, PNU-83892, in plasma was developed to characterize the enantioselective pharmacokinetics of PNU-83894, a potential anticonvulsant candidate. The method involves solid-phase extraction (phenyl column) of the enantiomers from plasma followed by direct enantioselective separation on a beta-cyclodextrin HPLC chiral column and UV detection at 230 nm. The linear range for this method was found to be 12.5 ng/ml to 5.00 microg/ml and the intra- and inter-assay precision and accuracy for each enantiomer were <11% in all cases. The validity of this assay was also demonstrated by its application to the pharmacokinetic evaluation of PNU-83894 in the dog.
Zhong
W Z
WZ
Drug Metabolism Research, Pharmacia & Upjohn, Kalamazoo, MI 49007-4940, USA. wei-zhu.zhong@am.pnu.com
Williams
M G
MG
D000818:Animals; D001549:Benzamides / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003514:Cyclohexylamines / Q000097:blood*; D004285:Dogs; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D001549:Benzamides; D003514:Cyclohexylamines; C080514:N-(2-aminocyclohexyl)-3,4-dichlorobenzamide; C080515:N-(2-methylaminocyclohexyl)-3,4-dichlorobenzamide