Development of a validated capillary electrophoresis method for enantiomeric purity testing of dexchlorpheniramine maleate

Eeckhaut, Ann Van; Detaevernier, M.R.; Michotte, Yvette

doi:10.1016/s0021-9673(02)00314-x

Cited by 30 publications

(22 citation statements)

References 25 publications

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“…1. The chiral separation of these compounds has been studied extensively [4,18,[21][22][23][24][25][26][27][28][29].…”

Section: Resultsmentioning

confidence: 99%

“…The capillary was temperature-controlled at 257C by liquid cooling. Sample solutions were introduced by pressure (0.5 psi) for 5 s, followed by a 1 s injection of water [18,19]. Between runs, the capillary was flushed (20 psi) for 2 min with water and for 3 min with run buffer.…”

Section: Ce Equipment and Conditionsmentioning

confidence: 99%

“…Moreover, they are all injected as their maleate salts. To investigate whether the presence of maleate was responsible for the observed effects, DM base was extracted from the maleate solution and then redissolved in 0.1 M HCl to form a hydrochloride salt (method adapted from [18,42]). Approximately the same profile was obtained for both salts (Figs.…”

Section: Influence Of Analyte Structurementioning

confidence: 99%

“…Moreover, CMCD will migrate towards the anode. This should increase the difference in electrophoretic mobility between the free and the complexed forms of the analyte enantiomers [6,8,18,24]. However, it was shown for DM [17] that the slight deprotonation of the carboxylic function was only partly responsible and that other mechanisms may also play a role.…”

Section: Influence Of Analyte Structurementioning

confidence: 99%

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Influence of methanol on the enantioresolution of antihistamines with carboxymethyl‐β‐cyclodextrin in capillary electrophoresis

et al. 2004

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According to the model of Wren and Rowe, the separation between two enantiomers in capillary electrophoresis (CE) decreases if an organic modifier is added to the run buffer containing a neutral cyclodextrin (CD) in a concentration below its optimal value in a solvent-free system. In previous work, however, it was observed that the addition of methanol to the background electrolyte (BGE) containing not charged carboxymethyl-beta-CD in a concentration below its optimal value, increased the enantioresolution of dimetindene maleate. The enantioresolution decreased when other organic modifiers (ethanol, isopropanol or acetonitrile) were added and/or when other neutral (beta-CD, hydroxypropyl-beta-CD) or chargeable (carboxyethyl-beta- and succinyl-beta-CD) CDs were used. In this CE study further attempts are made to elucidate the observed phenomena through investigating other basic drugs. The effect of organic modifier and CD concentration on the enantioseparation was studied by means of central composite designs. It is shown that obtaining this increase in enantioresolution depends upon the type of CD, the type of organic modifier, and the structure of the analytes. It was also observed that small differences in the structure of the analytes or the CD could have an influence on the enantioresolution. The addition of methanol also resulted in different effects on the resolution of closely related analytes.

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“…1. The chiral separation of these compounds has been studied extensively [4,18,[21][22][23][24][25][26][27][28][29].…”

Section: Resultsmentioning

confidence: 99%

Section: Ce Equipment and Conditionsmentioning

confidence: 99%

Section: Influence Of Analyte Structurementioning

confidence: 99%

Section: Influence Of Analyte Structurementioning

confidence: 99%

See 2 more Smart Citations

Influence of methanol on the enantioresolution of antihistamines with carboxymethyl‐β‐cyclodextrin in capillary electrophoresis

et al. 2004

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“…Furthermore, in CE, the resolution decreases when the separation system becomes overloaded. Therefore, an electrophoretic system giving nearly baseline resolution of a racaemate will not be fully able to resolve a minor and a major peak as relatively high resolution is required (Magnusson et al, 2002;Van Eeckhaut et al, 2002). It is generally accepted that a resolution of 1.5 corresponds to a baseline resolution for a racaemic mixture followed by the impurity, due to the triangular and (partially) overlapping main peak masking the impurity.…”

Section: Response Analysis-software Simulationmentioning

confidence: 99%

Enantiomeric impurity determination in capillary electrophoresis using a highly-sulfated cyclodextrins-based method

Matthijs

Heyden

2006

Biomed. Chromatogr.

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Capillary electrophoresis (CE), using highly-sulfated cyclodextrins as chiral selectors, has been applied to determine the chiral purity of pharmaceutical compounds. A chiral separation strategy, developed earlier for racaemic mixtures, was applied on four basic drugs (propranolol, atenolol, chlorpheniramine and tryptophan methylester). The aim was to develop validated separation methods which allow determination of 0.1% impurity levels of the unwanted enantiomers (distomer) in the presence of 99.9% of the active compound (eutomer). The linearity, quantification limits for the trace enantiomers and the precision of the measurements were determined. In a second part, impurity separations have been simulated in order to evaluate the required resolution when assaying impurities. It is shown that a baseline resolution of 1.5, generally accepted for racaemic mixtures, does not always allow good impurity determinations. Two alternative methods to solve this problem have been proposed.

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Determination of chlorpheniramine in human plasma by HPLC‐ESI‐MS/MS: application to a dexchlorpheniramine comparative bioavailability study

Moreno

Oliveira‐Silva

Sverdloff

et al. 2009

Biomedical Chromatography

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In the present study a fast, sensitive and robust validated method to quantify chlorpheniramine in human plasma using brompheniramine as internal standard (IS) is described. The analyte and the IS were extracted from plasma by LLE (diethyl ether-dichloromethane, 80:20, v/v) and analyzed by HPLC-ESI-MS/MS. Chromatographic separation was performed using a gradient of methanol from 35 to 90% with 2.5 mm NH(4)OH on a Gemini Phenomenex C(8) 5 microm column (50 x 4.6 mm i.d.) in 5.0 min/run. The method fitted to a linear calibration curve (0.05-10 ng/mL, R > 0.9991). The precision (%CV) and accuracy ranged, respectively: intra-batch from 1.5 to 6.8% and 99.1 to 106.6%, and inter-batch from 2.4 to 9.0%, and 99.9 to 103.1%. The validated bioanalytical procedure was used to assess the comparative bioavailability in healthy volunteers of two dexchlorpheniramine 2.0 mg tablet formulations (test dexchlorpheniramine, Eurofarma, and reference Celestamine, Schering-Plough). The study was conducted using an open, randomized, two-period crossover design with a 2 week washout interval. Since the 90% confidence interval for C(max) and AUC ratios were all within the 80-125% interval proposed by ANVISA and FDA, it was concluded that test and reference formulations are bioequivalent concerning the rate and the extent of absorption.

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Development of a validated capillary electrophoresis method for enantiomeric purity testing of dexchlorpheniramine maleate

Cited by 30 publications

References 25 publications

Influence of methanol on the enantioresolution of antihistamines with carboxymethyl‐β‐cyclodextrin in capillary electrophoresis

Influence of methanol on the enantioresolution of antihistamines with carboxymethyl‐β‐cyclodextrin in capillary electrophoresis

Enantiomeric impurity determination in capillary electrophoresis using a highly-sulfated cyclodextrins-based method

Determination of chlorpheniramine in human plasma by HPLC‐ESI‐MS/MS: application to a dexchlorpheniramine comparative bioavailability study

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