An experimental design methodology applied to the enantioseparation of a non-steroidal anti-inflammatory drug candidate.
An experimental design methodology has been applied to the enantioseparation of a new synthesized aryl propionic acid of pharmaceutical interest, namely 2-[(4'-benzoyloxy-2'-hydroxy)phenyl-propionic acid] (DF-1770y) by chiral capillary zone electrophoresis (CCZE). The chiral separation of the studied compound has been achieved employing vancomycin as the chiral selector. The partial filling-counter current method has been used in order to avoid the presence of the absorbing chiral selector in the path length of the detector and to increase the method sensitivity. A central composite design has been employed to optimize the experimental conditions for a fast separation of the enantiomers of the new synthesized aryl propionic acid. Critical parameters such as chiral selector concentration, pH and temperature have been studied to evaluate how they affected responses such as resolution and migration times. The desirability function approach has been employed in order to find the best compromise between the different experimental responses. The proposed CCZE method provided the baseline enantioseparation of the investigated drug. A Britton-Robinson buffer at pH 6.4 supplemented with 7 mM of vancomycin at 22 degrees C and -20 kV were the optimum experimental conditions allowing to achieve the highest enantioresolution of DF-1770y in less than 8.5 min.
Dipartimento di Scienze Farmaco-Biologiche, Università di Catanzaro Magna Graecia, Complesso Ninì Barbieri, 88021 Roccelletta di Borgia, Catanzaro, Italy.
R
R
Ficarra
P
P
Cutroneo
Z
Z
Aturki
S
S
Tommasini
M L
ML
Calabrò
R
R
Phan-Tan-Luu
S
S
Fanali
P
P
Ficarra
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification*; D019075:Electrophoresis, Capillary / Q000379:methods; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008962:Models, Theoretical; D011422:Propionates / Q000032:analysis*; D013237:Stereoisomerism; D013696:Temperature
C465860:2-((4'-benzoyloxy-2'-hydroxy)phenyl)propionic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007202:Indicators and Reagents; D011422:Propionates