Stereoselective Determination of (βS,γR and βR,γS)-4-[3-(4-Acetyl-3-hydroxy-2-propylphenoxy)propylthio]-γ-hydroxy-β-methylbenzenebutanoic Acid in Human and Rat Plasma by Normal-Phase High-Performance Liquid Chromatography

A Stereoselective high-performance liquid chromatographic method was developed for the determination of the enantiomeric composition comprising (βS,γR and βR,γS)-4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio]-γ-hydroxy-β-methylbenzenebutanoic acid (1) in human and rat plasma. Both enantiomers,...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 1987-02, Vol.76 (2), p.169-173
Main Authors: Slobodzian, Debra K., Hsieh, John Y-K., Young, Robert N., Bayne, William F.
Format: Article
Language:English
Subjects:
Analysis
Animals
Biological and medical sciences
Chromatography, High Pressure Liquid
General pharmacology
Humans
Kinetics
Magnetic Resonance Spectroscopy
Male
Medical sciences
Pharmacology. Drug treatments
Phenylbutyrates - blood
Rats
Species Specificity
Stereoisomerism
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Summary:A Stereoselective high-performance liquid chromatographic method was developed for the determination of the enantiomeric composition comprising (βS,γR and βR,γS)-4-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propylthio]-γ-hydroxy-β-methylbenzenebutanoic acid (1) in human and rat plasma. Both enantiomers, (βS,γR) and (βR,γS)-1, were isolated from the plasma by liquid-liquid extraction, the organic phase was evaporated to dryness, and the residue was lactonized with p-toluenesulfonic acid followed by derivatization with R(+)-α-methylbenzylamine to form diastereomeric Schiff base adducts. Separation was performed on a silica column (Supelcosil) with a mobile phase composed of 97.8% hexane, 2% isopropyl alcohol, and 0.2% trietnylamine. The column eluant was monitored with a variable wavelength UV detector set at 280nm (0.005 AUFS). Based on the peak area ratios, the method shows excellent linear relationships with their corresponding concentrations and satisfactory intraday and interday assay precision and accuracy. The detection limit of this method is 25ng/mL in plasma for each enantiomer. The method has been applied to the assay of plasma obtained from human subjects administered 1 in safety and tolerability studies and from rats administered 1 intravenously or per os.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600760218