Chiral resolution of the enantiomers of new selective CB(2) receptor agonists by liquid chromatography on amylose stationary phases.
Analytical HPLC methods using derivatized amylose chiral stationary phases, Chiralpak AD-H and Chiralpak AS, were developed for the direct enantioseparation of eight substituted 4-oxo-1,4-dihydroquinoline-3-carboxamide derivatives with one stereogenic center. Baseline separation (Rs>1.5) was always achieved on amylose based Chiralpak AD-H column to the difference with Chiralpak AS. Using UV detection, a linear response was observed within a 180-420 micromol L(-1) concentration range (r2>0.991) for three racemic compounds 1, 3 and 4 with best pharmacological potentials; repeatability, limit of detection (LD) and quantification (LQ) were also determined: LD varied, for the solutes, from 0.36 to 2.56 micromol L(-1). Finally, the enantiopurity of these compounds was determined. Additionally, the effect of temperature variations upon isomer separations was investigated.
Stern
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Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Université de LILLE 2-BP 83, 3 rue du Pr. Laguesse, 59006 Lille, France.
Goossens
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L
Vaccher
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C
Bonte
J-P
JP
Depreux
P
P
Henichart
J-P
JP
Goossens
J-F
JF
D000688:Amylose / Q000031:analogs & derivatives* / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D015394:Molecular Structure; D048448:Phenylcarbamates / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D013696:Temperature
D002219:Carbamates; D048448:Phenylcarbamates; D011804:Quinolines; D043885:Receptor, Cannabinoid, CB2; D012997:Solvents; C445088:chiralpak AS; C080033:Chiralpak AD; D000688:Amylose