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Selected Publication:
Egginger, G; Lindner, W; Kahr, S; Stoschitzky, K.
Stereoselective HPLC bioanalysis of atenolol enantiomers in plasma: application to a comparative human pharmacokinetic study.
Chirality. 1993; 5(7):505-512
Doi: 10.1002/chir.530050706
Web of Science
PubMed
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FullText_MUG
- Co-authors Med Uni Graz
- Stoschitzky Kurt
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- Abstract:
- An enantioselective HPLC bioassay has been developed relying on extraction of (R)- and (S)-atenolol from alkalinized plasma or serum (pH > 12) into dichloromethane containing 5% (v/v) 1-butanol followed by an achiral derivatization of the drug with phosgene leading to (R)- and (S)-oxazolidine-2-one derivatives. Under these conditions there was quantitative conversion of the acetamido group to the corresponding nitrile. These stable derivatives were separated on a (R,R)-diaminocyclohexane-dinitrobenzoyl chiral stationary phase [(R,R)-DACH-DNB] using dichloromethane/methanol 98/2 as mobile phase. Determination limits of 0.5 ng for (R)- and 0.6 ng for (S)-atenolol could be achieved using fluorimetric detection. The assay was applied to a human pharmacokinetic study which was performed in a randomized cross-over, double-blind fashion in 12 healthy volunteers, administering single oral doses of 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol. AUC0-24 and Cmax values of (R)-atenolol were slightly but significant higher than those of (S)-atenolol. The R/S ratios were 1.09 for AUC(R)/AUC(S) and 1.03 for Cmax (R)/Cmax(S) (P < 0.01) respectively after administration of the racemic drug. However, there were no difference between AUC, Cmax, and t1/2 values of each enantiomer, whether they were administered as single enantiomers or in the form of its racemic mixture.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Oral -
- Adult -
- Atenolol - blood
- Chromatography, High Pressure Liquid - methods
- Double-Blind Method - methods
- Female - methods
- Humans - methods
- Male - methods
- Regression Analysis - methods
- Stereoisomerism - methods
- Structure-Activity Relationship - methods
- Time Factors - methods
- Find related publications in this database (Keywords)
- Atenolol Enantiomers
- Enantioselective HPLC Bioassay
- Stereoselective Pharmacokinetics
- Oxazolidine-2-One Derivative
- Fluorometric Detection