Resolution of the enantiomers of ibuprofen; comparison study of diastereomeric method and chiral stationary phase method.
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.
Ahn
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Biopharmaceutic Research Branch, Food and Drug Administration, Washington, DC 20204.
Shiu
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Trafton
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Doyle
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TD
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D005563:Formic Acid Esters; D007052:Ibuprofen / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D007202:Indicators and Reagents; D011804:Quinolines; D013237:Stereoisomerism
D005563:Formic Acid Esters; D007202:Indicators and Reagents; D011804:Quinolines; C007658:ethyl chloroformate; C000470:EEDQ; D007052:Ibuprofen