6-O-(2-hydroxybutyl)-β-CD as a chiral selector for nonaqueous capillary electrophoretic separation of chiral drugs

Abstract

6-O-(2-hydroxybutyl)-β-CD, as a new β-cyclodextrin (β-CD) derivative, was successfully synthesized. It was used as a chiral selector to separate six chiral drugs, including propranolol, anisodamine, promethazine, ketoconazole, benzhexol, and fenfluramine in nonaqueous capillary electrophoresis (NACE). The effects of the organic solvent, the electrolytes, the concentrations of cyclodextrin derivatives, and the pH of the buffer on the chiral resolution (Rs) were investigated. The baseline separation of enantiomers, including propranolol (Rs = 2.26), anisodamine (Rs = 2.31), promethazine (Rs = 2.42), ketoconazole (Rs = 2.56), benzhexol (Rs = 3.38), and fenfluramine (Rs = 3.04), could be achieved using a buffer of 100 mmol$L -1 citric acid and 50 mmol$L -1 Tris (hydroxymethyl) aminomethane (Tris) at pH 4.6 containing 100 mmol$L -1 6-O-(2-hydroxybutyl)-β-CD in formamide (FA).

Pharmaceuticals and Related Drugs

“…During the last two years, several hundred papers have been published that deal with various aspects of chiral separations. A few examples of them include ones that use high performance liquid chromatography, − gas chromatography, thin-layer chromatography, , capillary electrochromatography, − capillary electrophoresis − and micellar and related electrokinetic methods − to resolve many different enantiomeric compounds by use of a chiral stationary phase, a chiral additive, or a chiral derivatizing reagent. Summarized in Table are examples of some of the compounds where chiral purity was evaluated in either the bulk pharmaceutical or the formulated product using one of these approaches.…”

Enantioseparation of fourteen amino alcohols by nonaqueous capillary electrophoresis using lactobionic acid/d-(+)-xylose–boric acid complexes as chiral selectors

“…13 Furthermore, the special physicochemical properties of the nonaqueous solvents facilitate the hyphenation to mass spectrometer (MS). 14 The most common chiral selectors used in NACE are cyclodextrins (CDs), [15][16][17][18] macrocyclic antibiotics, 19,20 chiral ion-pair complexes, [21][22][23][24] and so on. In our previous work, a series of D/Ltartrate-boric acid complexes and two polyols-boric acid complexes were in situ synthesized and used as chiral ion-pair selectors in NACE for the enantioseparation of some amino alcohols.…”

Nonaqueous Capillary Electrophoretic Enantioseparation of Water Insoluble Tröger's Base Derivatives Using β‐Cyclodextrin as Chiral Selector

“…10 The quality of the chiral separation can be influenced, similar as in the aqueous environment, by several other factors, mainly by acidity/alkalinity, ionic strength, and the presence of other solvents in the background electrolyte (BGE). [11][12][13][14] Until now NACE has been used with β-CD and its derivatives as chiral selector additives to BGE for enantioseparation of amino acids, 15 drugs, 9,10,14,16,17 1,3,4-thia and 1,3,4-selenadiazine derivates, 18 and pesticides. 19 Herein we describe the development of a method allowing for the enantioseparation of six Tröger's base (TB) derivatives ( Fig.…”

“…Until now NACE has been used with β‐CD and its derivatives as chiral selector additives to BGE for enantioseparation of amino acids, drugs, 1,3,4‐thia and 1,3,4‐selenadiazine derivates, and pesticides …”