abstract
The enantioseparation of chiral drugs is a major challenge for the pharmaceutical industry as the pharmacological activities of the enantiomers may differ, which can lead to severe secondary effects in the treatment of diseases. The aim of this study is to develop an enantioseparation platform for the resolution of ofloxacin (OFX) using enantioselective liquid-liquid extraction (ELLE) based on a hydrophobic eutectic solvent (HES) in conjunction with one chiral selector. beta-Cyclodextrin (beta-CD) derivatives, including beta-CD, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), carboxymethyl-beta-cyclodextrin sodium salt (CM-beta-CD), and sulfated-beta-cyclodextrin sodium salt (S-beta-CD), were investigated as potential chiral selector for the separation of (R/S-OFX), with CM-beta-CD proving to be the most promising. The efficiency of the HES-based ELLE system was then studied, and a total of fourteen systems were evaluated using HES from four groups: L-menthol: fatty acid, L-menthol: fatty alcohol, fatty acid: fatty acid, and fatty acid: fatty alcohols. Decanoic acid: dodecanoic acid (C10 acid: C12 acid) in a molar ratio of 2:1 was identified as the optimal HES-based ELLE system for the enantioseparation of R/S-OFX. This selected system was further used to optimize enantioseparation conditions, including pH, HES-water ratio (v/v), and excess of chiral selector (CM-beta-CD), using response surface methodology (RSM). Under optimal conditions, i.e., pH 3.6, HES-water ratio (v/v) of 1:2 and a 77-fold molar excess of chiral selector, an OFX selectivity (alpha) of 3.8 +/- 0.3 was achieved in a single-step.
keywords
BETA-CYCLODEXTRIN; CHIRAL SELECTOR; CAPILLARY-ELECTROPHORESIS; ENANTIOMERIC SEPARATION; DRUGS; SUBSTANCES; WATER; ACIDS
subject category
Engineering
authors
Moradi, M; Ferreira, AM; Neves, CMSS; Sosa, FHB; Pazuki, G; Coutinho, JAP
our authors
Ana Maria da Conceição Ferreira Takahashi
Junior Researcher
Catarina Maia Seco Seiça Neves
Assistant Researcher
Filipe Hobi Bordon Sosa
Junior Researcher
Projects
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)
acknowledgements
This work was developed partly within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI 10.54499/UIDB/50011/2020) , UIDP/50011/2020 (DOI 10.54499/UIDP/50011/2020) & LA/P/0006/2020 (DOI 10.54499/LA/P/0006/2020) , financed by national funds through the FCT/MCTES (PIDDAC) . AMF, CSSN and FHBS acknowledge FCT for the research contracts CEECIND/00361/2022 (DOI 10.54499/2022.00361.CEECIND/CP1720/CT0020) , CEECIND/01975/2017 (DOI 10.54499/CEECIND/01975/2017/CP1459/CT0037) and CEECIND/07209/2022 (DOI 10.54499/2022.07209.CEECIND/CP1720/CT0019) under the Scientific Stimulus - Individual Call, respectively.