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  • 1
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Diltiazem hydrochloride stereoisomers ; Chiralcel OF ; Chiral inversion ; Epimerization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary The simultaneous stereospecific assay of four stereoisomers of diltiazem hydrochloride in bulk drug and aqueous solution was developed using HPLC on a Chiralcel OF column. The four isomers were quantitated with good precision by the internal standard method. The chiral inversion of (+)-cis-diltiazem hydrochloride in vitro, stability of its (2S, 3S) configuration in the solid and aqueous states was examined by HPLC. Chiral inversion of (+)-cis-diltiazem hydrochloride was not observed in the solid state, and its (2S, 3S) configuration was stable to heat, humidity and light. Chiral inversion of (+)-cis-diltiazem hydrochloride (2S, 3S) was observed in aqueous solution under UV, but not in aqueous solution stored at 80°C for 5h nor under visible light for 10 h. The (+)-cis-diltiazem hydrochloride (2S, 3S) epimerized to (+)-trans-diltiazem hydrochloride (2R, 3S) with a half-life of 5h in aqueous solution under UV but the reverse chiral inversion of (+)-trans-diltiazem hydrochloride (2R, 3S) to (+)-cis-diltiazem hydrochloride (2S, 3S) was not observed.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Chromatographia 42 (1996), S. 617-630 
    ISSN: 1612-1112
    Keywords: Capillary zone electrophoresis ; Chiral separation ; Chiral selectors ; Dextran and dextrin ; Drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Polysaccharides such as dextrins, which are mixtures of linear α-(1,4)-linked D-glucose polymers, and dextrans, which are polymers of D-glucose units linked predominantly by α-(1,6) bonds, have been employed as chiral selectors in the capillary electrophoretic (CE) separation of enantiomers. Because these polymers are electrically neutral, the method is applicable to ionic compounds. Among the compounds tested the enantiomers of ibuprofen, naproxen, warfarin and the diltiazem synthetic intermediate 1,1′-binaphthyl-2,2′diyl hydrogen phosphate, which are anionic compounds, were successfully recognized by employing dextran or dextrin under neutral conditions. The enantiomers of basic or cationic drugs such as timepidium, primaquine, sulconazole, trimetoquinol, diltiazem and clentiazem were also successfully separated under acidic conditions. The effects of molecular mass and polysaccharide concentration on enantioselectivity were investigated. High concentrations of these polymers, especially dextrin, led to delayed migration times after repeated injections of the solutes into an uncoated capillary under neutral conditions. Consequently the capillary washing process was found to be very important to obtaining reproducible migration times in the system. A coated capillary was also investigated to overcome this problem. Finally, the method using electrically neutral polysaccharides was applied to the testing of the optical purity of the drug substances.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1612-1112
    Keywords: Capillary electrophoresis ; Aminoglycosidic antibiotics ; DEAE-dextran ; Drugs ; Enantiomer separation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Diethylaminoethyl (DEAE) dextran hydrochloride and three kinds of aminoglycosidic antibiotics; fradiomycin sulfate, kanamycin sulfate and streptomycin sulfate, were employed as chiral selectors in capillary electrophoresis, enantiomer separation. These selectors are cationic or basic because of amino functionality and therefore used for enantiomer separation of acidic compounds. To avoid adsorption of the basic or cationic selectors on the capillary inner surface, a coated capillary was employed. Among those tested, enantiomers of binaphthyl compounds and synthetic intermediates of diltiazem analogues were separated. Methanol addition was effective for the improvement of peak shape and resolution.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1612-1112
    Keywords: Column liquid chromatography ; Desacetyl diltiazem hydrochloride stereoisomers ; Chiralcel OF ; Chiral inversion ; Epimerization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary Direct resolution of four stereoisomers of the related compound of diltiazem hydrochloride, namely desacetyl diltiazem hydrochloride, was studied by both normal and reversed-phase chiral HPLC. The four stereoisomers were completely resolved on a Chiralcel OF column. The technique developed was applied to a chiral inversion study of desacetyl diltiazem hydrochloride. This inversion was observed neither in the solid state, in aqueous solution at 100°C for 3 h nor under visible light for 10h, but was observed in aqueous solution under UV irradiation. The (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride degraded with a half-life of 1.9 h in aqueous solution under UV and epimerized to (+)-(2R, 3S)-trans-desacetyl diltiazem hydrochloride. Similarly, (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride degraded about three times faster than diltiazem hydrochloride. Reverse epimerization of (+)-(2R, 3S)-trans-desacetyl diltiazem hydrochloride to (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride was not observed. The overall degradation was the result of two competitive processes, the epimerization and the decomposition of the benzothiazepin ring. The degradation and epimerization rate of (+)-(2S, 3S)-cis-desacetyl diltiazem hydrochloride in solution under UV depended upon the solvent, the aqueous pH, and concentration.
    Type of Medium: Electronic Resource
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