Chiral high-performance liquid chromatography methodology for quality control monitoring of dexfenfluramine

Li, Dou; Zeng, Jianing; Gerochi, Dante D.; Duda, Michael P.; Stuting, Hans H.

doi:10.1016/0021-9673(94)80580-6

Cited by 13 publications

(3 citation statements)

References 3 publications

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“…One method required derivatization 24 and the other method required a specific column. 26 A comparison of our results with those of chiral HPLC was thus not performed.…”

Section: Fenfluraminementioning

confidence: 99%

Quantitative ¹H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Salsbury

Isbester

2005

Magnetic Reson in Chemistry

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Determining the enantiomeric purity of chiral therapeutic agents is important in the development of active pharmaceutical ingredients (API). A strategy for determining the enantiomeric purity of three APIs was developed using nuclear magnetic resonance (NMR) and the chiral solvating agent (CSA) 1,1-bi-2-naphthyl (1). While chiral chromatography is widely used to evaluate enantiomeric purity, it can sometimes suffer from tedious sample preparation obviating rapid measurements that are sometimes needed during the manufacture of such agents. The techniques described herein provide comparable enantiomeric purity results with those obtained with traditional chiral HPLC and other published methods for these compounds. Chiral analysis of standard samples of methylbenzylamine enantiomeric mixtures using 1 were found to be quantitative to approximately 1% minor enantiomer. Enantiomeric purity determination by NMR utilizing chiral solvating agents do not require special instrumental techniques, chemical derivatization or standards and is therefore ideally suited for rapid routine analysis. As a result, the technique demonstrated is commonly used in our laboratory as a complementary or alternative method to chiral HPLC or optical rotation measurements for routine determination of enantiomeric purity.

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“…One method required derivatization 24 and the other method required a specific column. 26 A comparison of our results with those of chiral HPLC was thus not performed.…”

Section: Fenfluraminementioning

confidence: 99%

Quantitative ¹H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Salsbury

Isbester

2005

Magnetic Reson in Chemistry

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“…Over the past two decades, the ability to accomplish enantiomer separations chromatographically has become an extremely valuable analytical tool and, to a lesser extent, preparatively useful [1,2]. There are many important applications, particularly with respect to pharmaceuticals, ranging from quality control in production to monitoring the environmental fate of these materials [3,4].…”

Section: Introductionmentioning

confidence: 99%

Influence of the Azulene Ring on the Enantioseparation of 1,5-Diols

Horgen

Garner

2014

Chromatography

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The enantioseparation of a series of six azulene-centered 1,5-diol enantiomers was studied employing two cellulose-based chiral stationary phases under normal phase conditions (isopropanol/hexanes). The separations were generally quite good on Chiralcel-OD-H, with α values ranging from 1.2 to 8.4 (average 4.0) and resolution values of 0.4-8.3 (average 4.7). Only one of the six enantiomer pairs was not well resolved, but was well separated on Lux cellulose 2 (α 1.4, R s 8.7). It was observed that the enantioseparations of the RS/SR diastereomers (ave α = 7.8, R s = 8.2) were dramatically better than that of the corresponding RR/SS diastereomers (ave α = 2.1, R s = 3.0) on Chiralcel-OD-H. The better-resolved diastereomer pairs correspond to the more strongly retained diastereomers on silica gel. The enantiomers of two benzene 1,5-diols were much more poorly separated on both stationary phases, suggesting that the unusual polarity of the azulene ring enhances critical interactions with these phases.

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“…Thus the optimization of analytical separation methods for chiral compounds is needed in, for example, chiral drug purity control, pharmacokinetic studies etc. Analytical methods so far used for the analysis of enantiomers include high-performance liquid chromatography (HPLC), gas chromatography (GC), thin layer chromatography (TLC) and more recently capillary electrophoresis (CE) [3][4][5][6][7][8][9][10][11][12][13][14]. CE is a modern separation technique offering several advantages over some other in that it possesses high resolution power, allows rapid analysis with high efficiency using different separation modes, exhibits low costs and low pollution (only minute volumes of either buffer and samples are required) [15].…”

Section: Introductionmentioning

confidence: 99%

Experimental design methodologies to optimize the CE separation of epinephrine enantiomers

Fanali¹,

Furlanetto

Aturki³

et al. 1998

Chromatographia

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SummaryA capillary electrophoretic method using a chiral selector was optimized by experimental design for the enantioresolution of epinephrine enantiomers. Two 13-cyclodextrins derivatives, namely heptakis-2,6-di-O-methy|-13-cyclodextrin and carboxy-methyl-13-cyclodextrin, respectively neutral and charged, were used as chiral selectors employing an uncoated capillary. By using a statistical experimental design in which all factors are varied at the same time, it was possible to optimize the method with regard to the resolution between peaks and the two migration times. A fractional factorial design and a central composite design were used. A compromise between conflicting goals, such as maximization of resolution and minimization of analysis time, was found by means of a desirability function D. Balancing these goals against each other, the most acceptable solution to the problem was found and the optimized method gave a fast separation with complete resolution between the adrenaline enantiomers. The response surfaces obtained confirmed the robustness of the method.

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Chiral high-performance liquid chromatography methodology for quality control monitoring of dexfenfluramine

Cited by 13 publications

References 3 publications

Quantitative ¹H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Quantitative ¹H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Influence of the Azulene Ring on the Enantioseparation of 1,5-Diols

Experimental design methodologies to optimize the CE separation of epinephrine enantiomers

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Chiral high-performance liquid chromatography methodology for quality control monitoring of dexfenfluramine

Cited by 13 publications

References 3 publications

Quantitative 1H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Quantitative 1H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Influence of the Azulene Ring on the Enantioseparation of 1,5-Diols

Experimental design methodologies to optimize the CE separation of epinephrine enantiomers

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Quantitative ¹H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine

Quantitative ¹H NMR method for the routine spectroscopic determination of enantiomeric purity of active pharmaceutical ingredients fenfluramine, sertraline, and paroxetine