Investigation of Enantiomeric Separation of Chiral Drugs by CE Using Cu(II)–Clindamycin Complex as a Novel Chiral Selector

Wu, Jianfeng; Liu, Peng; Wang, Qingwei; Chen, Hui; Gao, Peng; Wang, Li; Zhang, Shengyong

doi:10.1007/s10337-011-2138-8

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…Currently, two common industrially applied techniques for the separation of two enantiomers are diastereomeric salt formation − and chiral chromatography. − The first is a relatively less costly process but can only be successfully applied when the compound of interest can easily be converted into a salt. In this case, addition of an enantiopure resolving agent leads to the formation of two distinct diastereomeric salts, which show dissimilar physical properties, allowing a chiral resolution through crystallization.…”

mentioning

confidence: 99%

Innovative Chiral Resolution Using Enantiospecific Co-Crystallization in Solution

Springuel

Leyssens

2012

Crystal Growth & Design

128

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Starting Materials. S-2-(2-oxopyrrolidin-1-yl)butanamide (Levetiracetam) (S-1) was purchased from Xiamen Top Health Biochem. Tech. Co., Ltd. S-Mandelic acid (S-2), R-mandelic acid (R-2), D-tartaric acid (S-3), and L-tartaric acid (R-3) were purchased from Acros Organics. (RS)-2-(2-oxopyrrolidin-1yl)butanamide (RS-1) was prepared from S-2-(2-oxopyrrolidin-1-yl)butanamide. 10g of S-2-(2oxopyrrolidin-1-yl)butanamide together with catalytic amount (0.05 eq) of MeONa were added to 10 ml of MeOH. The solution was kept at reflux under continuous stirring for 24h, and then cooled to room temperature. The compound crystallizes spontaneously. After filtration, the compound was washed twice with MeOH. The recovered compound was used as such.X-ray Powder Diffraction (XRPD). X-ray diffraction (XRD) measurements were performed with a Siemens D5000 difractometer equipped with a Cu X-ray source operating at 40kV and 40 mA and a secondary monochromater allowing to select the Kα radiation of Cu (λ = 1.5418 Å). A scanning range of 2θ values from 2° to 72° at a scan rate of 0.6° min -1 was applied.Differential Scanning Calorimetry (DSC). DSC measurements were performed on a DSC 821 Mettler Toledo. Prior to measurements, the DSC was calibrated using indium. Perforated aluminium crucibles were used for analysis. The heating rate was either 10 or 5°C min -1 over a range from 25°C to 140°C (alternatively to 180 °C if melting did not yet occur).High-performance liquid chromatography (HPLC). A reverse HPLC system Waters Alliance 2695 equipped with a PDA detector (Waters 2998) turned to 210 nm was used to monitor the Waters Atlantis T3 analytical column (50 mm x 4.6 mm x 3.5 µm). The injection volume was 10 µl and column temperature was keep at 35°C. A chiral HPLC system Waters 600 equipped with a PDA detector (Waters 996) set to 205 nm for detection. A Daicel Chiralpak IA analytical column (250 mm x 4.6 mm x 5 µm) has been used. An isocratic flow rate of 1 ml/min (80% Isohexane, 20% Ethanol) was used for elution. The injection volume was 25 µl and column temperature was keep at 20°C. In both systems, the columns are equilibrated in the initial conditions (for 10 min for reverse HPLC and for 30 min for chiral HPLC).Screening Experiment. The screening procedure consists in preparing a set of vials with given compositions of RS-1, S-1, and S-2. The screening is limited to the right part of the ternary phase diagram (the white part in Figure 2) because of a lack R-1. As R-1 shows no biological interest, this molecule is not marketed. A fixed molar percentage (89 mol%) of acetonitrile is added in each vial, which are then hermetically sealed. Vials are heated up to 60°C until complete dissolution. Vials were then stored at a given temperature and seeded with all of the possible solid states, i.e., RS-1 form I, S-1, S-2, and LSMA co-crystal. After two weeks, the system is assumed to have reached equilibrium.

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mentioning

confidence: 99%

Innovative Chiral Resolution Using Enantiospecific Co-Crystallization in Solution

Springuel

Leyssens

2012

Crystal Growth & Design

128

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“…The best results were obtained when using a BGE composed of 20 mM clindamycin/10 mM Cu 2+ at pH 9.06. The high adsorption of the complex to the capillary inner surface is the fundamental drawback of this chiral separation method [ 70 ].…”

Section: Antibiotics As Css In Cementioning

confidence: 99%

The Use of Antibiotics as Chiral Selectors in Capillary Electrophoresis: A Review

Hancu¹,

Papp²,

Szekely-Szentmiklosi³

et al. 2022

Molecules

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Chirality is becoming an essential issue in modern pharmaceutical research as regulatory agencies emphasize the safety and efficiency of enantiomers in drug development. The development of efficient and reliable chiral separation methods became a necessity in the last 30 years, and capillary electrophoresis (CE), due to its relatively low costs and “green” features, is attracting increased attention. Cyclodextrin (CD) and their derivatives are the most frequently used chiral selectors (CSs) in CE, however, the use of antibiotics as CSs represents an interesting alternative. Various classes of antibiotics (aminoglycosides, ansamycins, glycopeptides, lincosamides, macrolides, tetracyclines) have been used more or less successfully for the enantio-separation of pharmaceuticals. Antibiotics offer the possibility of a multitude of potential interactions (electrostatic, inclusion, hydrogen bonding, etc.) due to their chemical diversity, allowing the enantio-separation of analytes with a wide range of structural characteristics. This article aims to review the application of various classes of antibiotics in the CE enantio-separation of pharmaceuticals. Antibiotic physiochemical characteristics, variables impacting enantio-separation, advantages, and disadvantages when certain antibiotics are used as CSs in CE are also explored.

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“…The novel chiral selector clindamycin phosphate, a lincosamide antibiotic, was evaluated for enantioseparation capability toward basic drugs (propranolol and metoprolol) . Wu et al described a CZE method based on ligand‐exchange mechanism using a novel ternary complex of Cu(II)–clindamycin as chiral selector for the chiral separation of some racemic drugs enantiomers. Clindamycin, which contains amino, hydroxy, and carbonyl moieties in its structure, can interact with metal ions via its N, O, and/or S atom in complexation reactions and act as a tridentate ligand.…”

Section: Enantioseparation Of β‐Blockers By Means Of Capillary Electrmentioning

confidence: 99%

Recent developments in chiral analysis of β‐blocker drugs by capillary electromigration techniques

Zhang

Chen

et al. 2014

Electrophoresis

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The latest developments in chiral analysis of β-blocker drugs by capillary electromigration techniques are reviewed in this article. Following the previous review by Aturki et al. [Electrophoresis 2011, 32, 2602-2628], this review includes the papers published during the period from January 2011 to December 2013. During this time, some novel chiral selectors were reported and applied to improve the enantioseparation of β-blocker drugs and structurally related compounds. These chiral selectors include CDs and their derivatives, macrocyclic antibiotics, tartrate complexs, the monolithic molecularly imprinted polymer, and the polymeric surfactants. In addition, this article summarizes the methodological improvements for enhancing sensitivity in chiral analysis of β-blockers and structurally related compounds by CE. The involved authors described the use of online sample preconcentration techniques to increase the detection sensitivity in the enantiomeric analysis of a broad range of samples.

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Investigation of Enantiomeric Separation of Chiral Drugs by CE Using Cu(II)–Clindamycin Complex as a Novel Chiral Selector

Cited by 8 publications

References 27 publications

Innovative Chiral Resolution Using Enantiospecific Co-Crystallization in Solution

Innovative Chiral Resolution Using Enantiospecific Co-Crystallization in Solution

The Use of Antibiotics as Chiral Selectors in Capillary Electrophoresis: A Review

Recent developments in chiral analysis of β‐blocker drugs by capillary electromigration techniques

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