TY - JOUR

T1 - Development of a capillary electrophoretic method for determination of ketorolac enantiomers in human plasma using cationic β-cyclodextrin derivative as a chiral selector

AU - Kravchenko, Anastasia V

AU - Kolobova, Ekaterina A

AU - Kechin, Arseniy A

AU - Kartsova, Liudmila A

N1 - © 2022 Wiley-VCH GmbH.

PY - 2023/1

Y1 - 2023/1

N2 - A novel approach for the separation of ketorolac enantiomers by capillary electrophoresis is presented. A cationic β-cyclodextrin derivative based on imidazole was synthesized and used as a chiral selector in the background electrolyte. The influence of pH and ionic strength of background electrolyte, as well as cationic β-cyclodextrin derivative concentration on the resolution of ketorolac enantiomers, was investigated. The highest value of the resolution for ketorolac enantiomers was 1.46 when the background electrolyte consisted of 25 mM NaH2 PO4 (pH 6.4) with 1 mM 1-butyl-3-β-cyclodextrinimidazolium tosylate. Additionally, the possibilities of cationic derivatives for the separation of ketoprofen enantiomers were shown (peak resolution 1.06). The two-step preconcentration mode was developed to reduce the limit of detection of individual enantiomers. The proposed approach was successfully applied to determine ketorolac enantiomers in tablet "Ketorol express" and human plasma. The calibration range of ketorolac enantiomers for plasma samples was 0.25-2.50 μg/ml with coefficients of determination ≥ 0.99. The relative standard deviation both of the peak area and migration time was less than 15%, as well as the accuracy ranged from 90.1% to 110.2% for both analytes. The limits of detection were 44 and 55 ng/ml for R- and S-ketorolac. The quantity of ketorolac in plasma was verified with high-performance liquid chromatography.

AB - A novel approach for the separation of ketorolac enantiomers by capillary electrophoresis is presented. A cationic β-cyclodextrin derivative based on imidazole was synthesized and used as a chiral selector in the background electrolyte. The influence of pH and ionic strength of background electrolyte, as well as cationic β-cyclodextrin derivative concentration on the resolution of ketorolac enantiomers, was investigated. The highest value of the resolution for ketorolac enantiomers was 1.46 when the background electrolyte consisted of 25 mM NaH2 PO4 (pH 6.4) with 1 mM 1-butyl-3-β-cyclodextrinimidazolium tosylate. Additionally, the possibilities of cationic derivatives for the separation of ketoprofen enantiomers were shown (peak resolution 1.06). The two-step preconcentration mode was developed to reduce the limit of detection of individual enantiomers. The proposed approach was successfully applied to determine ketorolac enantiomers in tablet "Ketorol express" and human plasma. The calibration range of ketorolac enantiomers for plasma samples was 0.25-2.50 μg/ml with coefficients of determination ≥ 0.99. The relative standard deviation both of the peak area and migration time was less than 15%, as well as the accuracy ranged from 90.1% to 110.2% for both analytes. The limits of detection were 44 and 55 ng/ml for R- and S-ketorolac. The quantity of ketorolac in plasma was verified with high-performance liquid chromatography.

KW - Humans

KW - Ketorolac

KW - Electrophoresis, Capillary/methods

KW - Stereoisomerism

KW - Electrolytes

KW - Cyclodextrins/chemistry

KW - chiral selector

KW - electrokinetic chromatography

KW - enantiomers

KW - cyclodextrins

KW - on-line preconcentration

UR - https://www.mendeley.com/catalogue/42bc69ee-a7ac-3e80-bae2-35e9aaffbc92/

U2 - 10.1002/jssc.202200601

DO - 10.1002/jssc.202200601

M3 - Article

C2 - 36420913

VL - 46

SP - e2200601

JO - Journal of Separation Science

JF - Journal of Separation Science

SN - 1615-9306

IS - 2

ER -