Capillary Electrophoresis Chiral Separation for Enantiomeric Purity Determination of a Basic Drug in Pharmaceutical Formulations

Capillary electrophoresis using a running buffer composed of β-cyclodextrin as the chiral selector and ethanolamine mesylate at pH 9.6 is being used to monitor the stereochemical stability of a hydrophobic drug, containing two chiral centers, in two different formulated self-emulsifying drug delivery system (SEDDS) products. The separation takes place in less than 25 min. Strategies for enhancing the method reproducibility and detection sensitivity in the lower potency formulation are presented. The results demonstrating the specificity, assay precision, recovery, linearity and range achieved during the method validation experiments are presented in this paper.Presented at: CE in the Biotechnology and Pharmaceutical Industries: 7th Symposium on the Practical Applications for the Analysis of Proteins, Nucleotides and Small Molecules, Montreal, Canada, August 12–16, 2005.     

A Large Conformational Change of a Bridged b-Cyclodextrin Dimer in Aqueous Solution

As artificial enzymes, the binding constants of cyclodextrins (CDs) and their substrates are expected to be high1. For this purpose, many kinds of bridged cyclodextrin dimers2 whose two cyclodextrins are linked by various spacers have been constructed. It was of interest to make the dimers, whose binding constants would exceed 108dm3/mol3. Up to date, the bridged cyclodextrin dimers have been extensively studied as enzyme models and as molecular receptors4-6. Recently, we synthesized a brid…     

Preparation of a cyclodextrin dimer linked with a bis(picolinyl)cystine moiety and its intra- and intermolecular inclusion behavior

A novel cyclodextrin (CD) dimer linked with a bis(picolinyl)cystine (Cys) moiety was prepared by the coupling of Boc-protected Cys with amino-modified CDs, followed by deprotection of the Boc groups and bispicolinylation. The dimer showed less affinity to an organic guest molecule compared to that of a native CD monomer. It was attributed to an intramolecular inclusion of the pyridine moiety into CD cavity. The dimer caused significant increase of its organic guest affinity by an addition of a copper ion. The included pyridine group may come out of a CD cavity to bind the copper ion and the two CDs included cooperatively and intermolecularly a guest molecule with high affinity.     

Chiral separations by host-guest complexation with cyclodextrin and crown ether in capillary zone electrophoresis

Summary Capillary zone electrophoresis using cyclodextrins and a chiral crown ether as buffer constituents was studied for the enantiomeric separation of drugs and amino acids. Based on results obtained from separation of racemic -amino acids both chiral selectors are compared with respect to resolution, efficiency and retention time. For (±)-Quinagolide effects of buffer composition and temperature are examined using -cyclodextrin as chiral agent. Optimum conditions were pH 2.5 at 30 mmol L^–1 -cyclodextrin. A linear dependence of retention on -cyclodextrin concentration allowed calculation of formation constants of the host-guest complexes. Buffer concentration and temperature also influence resolution. The application of a chiral crown ether to the separation of optical isomers in capillary zone electrophoresis is described for the first time. Chiral recognition of solutes depends on the formation of protonated alkyl amines and separation is attributed to the formation of diastereomeric host-guest complexes with different interactions for each enantiomer. The effects of crown ether concentration on resolution are presented.     

Synthesis of Some Allyl-β-Cyclodextrin Derivatives and their Properties as Capillary GC Stationary Phases

Summary Three -Cyclodextrin derivatives (-CDs) were synthesized by substituting the 2,6-OH groups of -CD with allyl groups and the 3-OH groups with three different acyl groups (valeryl, heptanonyl, octanoyl). The chromatographic properties of these -CDs as stationary phases for capillary gas chromatography (CGC) were studied. The test results showed that the three -CDs possessed good coating properties and that the capillary columns coated with them exhibited high column efficiency. These -CDs can separate not only the disubstituted benzene isomers but also some racemic compounds.     

A Large Conformational Change of a Bridged β-Cyclodextrin Dimer in Aqueous Solution

A novel bridged β-CD dimer in which two β-cyclodextrins were linked by a naphthalene at positions 2 and 7 has been synthesized. 1H and 13CNMR measurements showed that a large change in the conformation of the dimer occurred in aqueous solution. The dimer interacted with methyl and ethyl orange to form stable inclusion complexes via "induced fit" mechanism.     

Chiral separation of the four stereoisomers of a novel antianginal agent using a dual cyclodextrin system in capillary electrophoresis

Reported here is an analytical method enabling the stereochemical resolution of a new antianginal compound possessing two stereogenic centers, leading to four stereoisomers. Only one of these isomers is currently under development as a novel antianginal agent and consequently, the other three isomers are considered as unwanted chiral impurities. Therefore, an enantioselective method is required in order to check its enantiomeric purity. This paper presents a method exploiting the high efficiency of capillary electrophoresis and the complexing properties of cyclodextrins to achieve the separation of the four stereoisomers of this weakly basic compound (pKa = 7.4). For this purpose, the combination of a neutral cyclodextrin, hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD), and an anionic cyclodextrin, carboxymethyl-beta-cyclodextrin (CM-beta-CD), was added to the separation buffer running in an uncoated silica capillary. After selection of the suitable cyclodextrin system, satisfactorily separation conditions were as follows: 30 mM phosphate buffer (pH 6.4) containing 10 mM of HP-gamma-CD and 10 mM of CM-beta-CD, running voltage +30 kV. The resulting run time and resolutions were respectively about 17 min and between 1.95 and 2.84. Linearity curves (0.993 < r2 < 0.998) are also shown.     

Heptakis(6-deoxy-6-guanidino)-β-cyclodextrin: an artificial model for mitochondrial ADP/ATP carrier

Heptakis(6-deoxy-6-guanidino)-β-cyclodextrin, prepared by one-step reaction of heptakis(6-amino-6-deoxy)-β-cyclodextrin with 1H-pyrozolecarboxamidine, binds ADP/ATP very tightly.