Determination of esmolol and metabolite enantiomers within human plasma using chiral column chromatography.
A high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of each of esmolol's enantiomers at the 25-1000 ng/ml concentrations observed in human plasma upon intravenous administration of this rapidly metabolized beta-adrenergic receptor blocking agent. Alternatively, a high performance liquid chromatography (HPLC) UV detection method has been developed for the simultaneous determination of each of the enantiomers for esmolol's metabolite which, in turn, achieve 2.5-50 microg/ml concentrations in human plasma. Utilizing chiral columns, these methods do not require a precolumn asymmetric derivatization step. Linearity in all cases was >0.99. Precision and accuracy at all but the lowest concentrations were within +/-6% for the esmolol enantiomers and within +/-2.5% for the esmolol metabolite enantiomers. These values should be suitable for performing thorough pharmacokinetic studies for all of the stereoisomers of this prototypical soft drug and its corresponding metabolite.
Fang
Lei
L
Department of Medicinal and Biological Chemistry, Center for Drug Design and Development, University of Toledo, College of Pharmacy, Toledo, OH 43606, USA.
Bykowski-Jurkiewicz
Crystal
C
Sarver
Jeffrey G
JG
Erhardt
Paul W
PW
D058671:Adrenergic beta-1 Receptor Antagonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D016014:Linear Models; D011412:Propanolamines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D058671:Adrenergic beta-1 Receptor Antagonists; D011412:Propanolamines; C036604:esmolol