TY - JOUR
T1 - Mechanistic insights on chaotropic interactions of liophilic ions with basic pharmaceuticals in polar ionic mode liquid chromatography
AU - Sanganyado, Edmond
AU - Lu, Zhijiang
AU - Gan, Jay
N1 - Funding information: E. Sanganyado is supported by the Fulbright Foreign Student Scholarship Program.
PY - 2014/11/14
Y1 - 2014/11/14
N2 - We report for the first time the effect of liophilic mobile phase additives on the mechanism of chiral recognition of basic chiral pharmaceutical on a vancomycin based chiral stationary phase (CSP). Using methanol as the mobile phase and 0.005% formic acid as pH modifier, we evaluated the effect of different concentrations of three types of liophilic anions, formate (HCOO−), nitrate (NO3−), and acetate (CH3COO−), on enantioresolution (Rs), enantioselectivity (α) and retention factor (k) of enantiomers of fluoxetine and atenolol. The effect of liophilic ion types on k followed the Hofmeister series: CH3COO− > HCOO− > NO3−. Increasing concentration from 4 to 20 mM resulted in decreases in Rs and k in accordance to hydrophobicity of the liophilic anion. The effect of temperature or mobile phase composition on enantioseparation was determined at 13–40 °C. For both analytes, standard changes in enthalpy (ΔH°) and entropy (ΔS°) calculated using van’t Hoff plots (ln k against 1/T) to varied from −4.99 to −0.63 kJ/mol and −11.82 to 9.47 J/mol, respectively. The van’t Hoff plots showed elution order of the enantiomers of each analyte did not reverse in the temperature range studied. Chiral recognition of the enantiomers of atenolol and fluoxetine in the presence of liophilic ions was enthalpy driven.
AB - We report for the first time the effect of liophilic mobile phase additives on the mechanism of chiral recognition of basic chiral pharmaceutical on a vancomycin based chiral stationary phase (CSP). Using methanol as the mobile phase and 0.005% formic acid as pH modifier, we evaluated the effect of different concentrations of three types of liophilic anions, formate (HCOO−), nitrate (NO3−), and acetate (CH3COO−), on enantioresolution (Rs), enantioselectivity (α) and retention factor (k) of enantiomers of fluoxetine and atenolol. The effect of liophilic ion types on k followed the Hofmeister series: CH3COO− > HCOO− > NO3−. Increasing concentration from 4 to 20 mM resulted in decreases in Rs and k in accordance to hydrophobicity of the liophilic anion. The effect of temperature or mobile phase composition on enantioseparation was determined at 13–40 °C. For both analytes, standard changes in enthalpy (ΔH°) and entropy (ΔS°) calculated using van’t Hoff plots (ln k against 1/T) to varied from −4.99 to −0.63 kJ/mol and −11.82 to 9.47 J/mol, respectively. The van’t Hoff plots showed elution order of the enantiomers of each analyte did not reverse in the temperature range studied. Chiral recognition of the enantiomers of atenolol and fluoxetine in the presence of liophilic ions was enthalpy driven.
KW - Chaotropic effect
KW - Chiral chromatography
KW - Enantioseparation
KW - Vancomycin based column
KW - Basic pharmaceuticals
KW - Liophilic ions
U2 - 10.1016/j.chroma.2014.09.054
DO - 10.1016/j.chroma.2014.09.054
M3 - Article
VL - 1368
SP - 82
EP - 88
JO - Journal of Chromatography A
JF - Journal of Chromatography A
SN - 0021-9673
ER -