Simultaneous determination of the elimination profiles of the individual enantiomers of racemic isoproterenol using capillary electrophoresis and microdialysis sampling.
Microdialysis sampling and capillary electrophoresis with electrochemical detection (CE-EC) were used in combination to simultaneously define the elimination profile of each enantiomer of isoproterenol (ISP) administered as a racemic mixture to Sprague-Dawley rats. Resolution of the enantiomers of ISP was accomplished using a running buffer containing methyl-O-beta-cyclodextrin as a chiral recognition reagent. The CE-EC system provided a concentration limit of detection of 0.63 ng ml-1, allowing monitoring of the elimination of ISP for up to six half-lives. Microdialysis sampling was capable of continuously monitoring the concentration of ISP with 60 s resolution. The concentration versus time data for the elimination of (+) and (-) ISP were fit to a biphasic first order elimination model yielding average apparent distribution half-lives of 0.52 +/- 0.07 min and 0.55 +/- 0.08 min and average apparent elimination half-lives of 9.8 +/- 2.2 and 8.8 +/- 2.0 min for (-) and (+) ISP, respectively (n = 3 rats). No statistically significant difference in the average half-lives was found. However, because each enantiomer was simultaneously determined in each animal a paired two-sample t-Test could also be done. This statistical analysis demonstrated that a difference in the elimination half-lives of the enantiomers of ISP does exist.
Hadwiger
M E
ME
Department of Chemistry, University of Kansas, Lawrence 66045, USA.
Park
S
S
Torchia
S R
SR
Lunte
C E
CE
D000318:Adrenergic beta-Agonists / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D019075:Electrophoresis, Capillary / Q000379:methods; D006207:Half-Life; D007545:Isoproterenol / Q000097:blood / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis / Q000379:methods; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013237:Stereoisomerism
D000318:Adrenergic beta-Agonists; D001798:Blood Proteins; D007545:Isoproterenol