Direct chiral separations of the enantiomers of phenylpyrazole pesticides and the metabolites by HPLC

Abstract

The enantiomeric separation of the enantiomers of three phenylpyrazole pesticides (fipronil, flufiprole, ethiprole) and two fipronil metabolites (amide-fipronil and acid-fipronil) were investigated by high-performance liquid chromatography (HPLC) with a CHIRALPAK IB chiral column. The mobile phase was n-hexane or petroleum ether with 2-propanol or ethanol as modifier at a flow rate of 1.0 mL/min. The influences of mobile phase composition and column temperature between 15 and 35°C on the separations were studied. All the analytes except ethiprole obtained complete enantiomeric separation after chromatographic condition optimization. Fipronil, flufiprole, amide-fipronil, and acid-fipronil obtained complete separation with the best resolution factors of 2.40, 3.40, 1.67, and 16.82, respectively, but ethiprole showed no enantioselectivity under the optimized conditions. In general, n-hexane with 2-propanol gave better separations in most cases. The results showed decreasing temperature and content of modifier in the mobile phase resulted in better separation and longer analysis time as well. The thermodynamic parameters calculated according to linear the Van't Hoff equation indicated the chiral separations in the study were enthalpy-driven. Fipronil and its two chiral hydrolyzed metabolites obtained baseline separation simultaneously under optimized conditions.

Liquid chromatographic separation and thermodynamic investigation of lorcaserin hydrochloride enantiomers on immobilized amylose–based chiral stationary phase

“…This gives Van't Hoff equation, which gives the clear way for straightforward determination of thermodynamic parameter of enantioseparation, such as the standard enthalpy (ΔH) and entropy (ΔS) of transfer of the solute from the mobile phase to the CSP where k represents the retention factor; R is the universal gas constant (8.3144 J/[mol·K]); T is the absolute temperature; ΔH and ΔS are the molar enthalpy and molar entropy of the adsorption; ΔΔH and ΔΔS are the differences ΔH2– ΔH1 and ΔS2–S1; and Φ is the column phase ratio.…”

“…This gives Van't Hoff equation, which gives the clear way for straightforward determination of thermodynamic parameter of enantioseparation, such as the standard enthalpy (ΔH) and entropy (ΔS) of transfer of the solute from the mobile phase to the CSP. [21][22][23] In…”

Study of the enantiomeric separation of the anticholinergic drugs on two immobilized polysaccharide‐based chiral stationary phases by HPLC and the possible chiral recognition mechanisms

“…The interaction forces between the analytes and stationary phase could be determined by the absolute value of ΔΔH° . The chiral recognition only depended on the steric hindrance when the absolute value of ΔΔH° was less than 0.1 kcal/mol.…”

Separation of eight bedaquiline analogue diastereomers by HPLC on an immobilized polysaccharide‐based chiral stationary phase

“…And as ΔΔ H ° is between 0.5 and 1.0 kcal/mol, the chiral recognition is not only related to the steri‐chindrance, but also to the other interactions, such as weak hydrogen bonding and π‐π interaction. And when the ΔΔ H ° value is greater than 1.0 kcal/mol, this indicates that the hydrogen bonding and π‐π interaction play the leading role . Thus, we could conclude that the diastereoseparation of compounds 4, 6, and 8 was mainly related to the steric hindrance, the weaker hydrogen bonding, and π‐π interaction.…”

“…And when the ΔΔH°value is greater than 1.0 kcal/mol, this indicates that the hydrogen bonding and π-π interaction play the leading role. 26,27 Thus, we could conclude that the diastereoseparation of compounds 4, 6, and 8 was mainly related to the steric hindrance, the weaker hydrogen bonding, and π-π interaction. And the diastereoseparation of compounds 1, 2, 5, and 7 was mainly affected by the stronger π-π and hydrogen bonding interaction.…”