Resolution of the enantiomers of ibuprofen; comparison study of diastereomeric method and chiral stationary phase method

• Published in: Journal of chromatography. B, Biomedical applications Biomedical applications, 1994-03, Vol.653 (2), p.163-169
• Main Authors: Ahn, Hae-Young, Shiu, Gerald K., Trafton, Walter F., Doyle, Thomas D.
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Dogs; Formic Acid Esters; General pharmacology; Ibuprofen - chemistry; Ibuprofen - isolation & purification; Ibuprofen - pharmacokinetics; Indicators and Reagents; Medical sciences; Pharmacology. Drug treatments; Quinolines; Stereoisomerism
• ISSN: 0378-4347; 1572-6495
• DOI: 10.1016/0378-4347(93)E0425-P

In this study, an indirect diastereomeric method and a direct method utilizing a chiral stationary phase (CSP) were investigated for the resolution of ibuprofen enantiomers. In the indirect method, ethylchloroformate (ECF) and 2-ethoxy-1-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) were utilized as first-step derivatizing reagents in acetonitrile or toluene. In the direct CSP method, ibuprofen enantiomers were derivatized to p-nitrobenzyl ureides and then resolved on an ( R)-(−)-(1-naphthyl)ethylurea CSP column. The derivatization procedure took place in 10 min with an overall inversion efficiency of 90.3%. Racemization was not observed under the derivatization conditions used. The HPLC-CSP method was utilized to study the pharmacokinetics of ibuprofen enantiomers in dog plasma after a single oral administration of 200 mg of ibuprofen racemate.