Multivariate optimisation approach for the separation of water-soluble vitamins and related compounds by capillary electrophoresis

Poster (1999)

Method development and validation for the LC quantitative analysis of bacitracin in a pharmaceutical formulation

Poster (1999)

Determination of copper, iron and zinc in pharmaceutical formulations by capillary electrophoresis

Poster (1999)

Elimination of adsorption effects in the analysis of water-soluble vitamins in pharmaceutical formulations by capillary electrophoresis.

in Journal of Chromatography. A (1999), 853(1-2), 391-401

A tendency to an increase in migration times was observed when different water-soluble vitamins were analysed repeatedly in pharmaceutical preparations by capillary electrophoresis. In order to better ... [more ▼]

A tendency to an increase in migration times was observed when different water-soluble vitamins were analysed repeatedly in pharmaceutical preparations by capillary electrophoresis. In order to better understand the origin of this effect, the influence of the vitamins and the excipients, such as cellulose derivatives, was investigated. These studies indicated that the increase in analyte migration times was most probably due to the adsorption of different kinds of constituents to the capillary wall. Different rinsing procedures were tested in order to eliminate these unfavourable effects. A rinse of the capillary with a 25 mM sodium dodecyl sulfate (SDS) solution in the running buffer between successive runs was found to be particularly effective when the analysis was performed by free solution capillary zone electrophoresis (CZE). When the vitamins were determined by micellar electrokinetic chromatography (MEKC) using SDS as surfactant, a short capillary rinse with the running buffer was sufficient to obtain reproducible migration times. The CZE and MEKC methods developed were validated and compared. Both methods could be applied to the determination of water-soluble vitamins in different multivitamin formulations. [less ▲]

The SFSTP guide on the validation of chromatographic methods for drug bioanalysis: from the Washington Conference to the laboratory

in Analytica Chimica Acta (1999), 391(2), 135-148

On the basis of the guidelines given in the Washington Conference report and the ICH (International Conference of Harmonisation) recommendations some suggestions about experimental design and data ... [more ▼]

On the basis of the guidelines given in the Washington Conference report and the ICH (International Conference of Harmonisation) recommendations some suggestions about experimental design and data evaluation are proposed by an SFSTP Commission dedicated to the validation of chromatographic methods in bioanalysis. In a series of meetings, members of this Commission have tried to elaborate a rational, practical and statistically reliable strategy to assure the quality of the analytical results generated. This strategy has been formalised in a guide and the main suggestions made by the Commission are summarised in the present paper. The SFSTP guide has been produced to help analysts from the pharmaceutical industry to validate their bioanalytical methods, It is the result of a consensus between professionals having expertise in bioanalytical and/or statistical fields. The suggestions presented in this paper should therefore help the analyst to design and perform the minimum number of validation experiments needed to obtain all the required information to establish and demonstrate the reliability of its analytical procedure. The SFSTP guide suggests a validation strategy in two steps: a pre-validation and the validation itself. An experimental design is described for each of these steps and the main aspects discussed in the paper are related to the selection of the most appropriate calibration model to fit experimental data and the most suitable way to determine the limit(s) of quantitation and subsequently the calibration range as well as the optimum number of experiments to be performed in the validation phase. (C) 1999 Elsevier Science B.V. All rights reserved. [less ▲]

Simultaneous Determination of Methylphenobarbital Enantiomers and Phenobarbital in Human Plasma by on-Line Coupling of an Achiral Precolumn to a Chiral Liquid Chromatographic Column

in Journal of Chromatography. A (1998), 819(1-2), 143-53

A fully automated liquid chromatographic (LC) method for the simultaneous determination of methylphenobarbital enantiomers and phenobarbital in human plasma has been developed. The method is based on the ... [more ▼]

A fully automated liquid chromatographic (LC) method for the simultaneous determination of methylphenobarbital enantiomers and phenobarbital in human plasma has been developed. The method is based on the use of a precolumn packed with an internal-surface reversed-phase packing material (LiChrospher ADS) for sample clean-up coupled to LC analysis on a cellulose tris(4-methylbenzoate) based chiral stationary phase (Chiralcel OJ-R). A 100-microliter plasma sample was injected directly on the precolumn packed with LiChrospher RP-18 ADS using a mixture of pH 5.0 phosphate buffer-methanol (97:3, v/v) as washing liquid. The analytes were then eluted in the back-flush mode with the LC mobile phase. The enantiomeric separation of methylphenobarbital was achieved on Chiralcel OJ-R). The retention times were modelled using a D-optimal design with ten experimental points in order to optimise the LC mobile phase for the separation of phenobarbital from the enantiomers of mephobarbital. The factors selected were the acetonitrile content, the pH and the sodium perchlorate concentration in the mobile phase. A Derringer's desirability function was used to find an optimal and robust solution within the experimental domain. The mobile phase selected consisted of a mixture of pH 7.0 phosphate buffer-acetonitrile (60:40, v/v). The elution profiles of phenobarbital, methylphenobarbital and blank plasma samples on the precolumn and the time needed for analyte transfer from the precolumn to the analytical column were then determined. Finally, the method developed was validated. [less ▲]

Method development and validation for the individual quantitation of drug en-antiomers using liquid chromatography or capillary electrophoresis

Conference (1998)

Validation of an automated method for the LC determination of atenolol in plasma : application of a new validation strategy

in Journal de Pharmacie de Belgique (1998), 53

Influence of cyclodextrins on the solubility and the pharmacokinetics of albendazole

Poster (1998)

Automated Determination of Tramadol Enantiomers in Human Plasma Using Solid-Phase Extraction in Combination with Chiral Liquid Chromatography

in Journal of Chromatography. B : Biomedical Sciences and Applications (1997), 698(1-2), 161-70

A sensitive and automated method for the separation and individual determination of tramadol enantiomers in plasma has been developed using solid-phase extraction (SPE) on disposable extraction cartridges ... [more ▼]

A sensitive and automated method for the separation and individual determination of tramadol enantiomers in plasma has been developed using solid-phase extraction (SPE) on disposable extraction cartridges (DECs) in combination with chiral liquid chromatography (LC). The SPE operations were performed automatically by means of a sample processor equipped with a robotic arm (ASPEC system). The DEC filled with ethyl silica (50 mg) was first conditioned with methanol and phosphate buffer, pH 7.4. A 1.0-ml volume of plasma was then applied on the DEC. The washing step was performed with the same buffer. The analytes were eluted with 0.15 ml of methanol, and 0.35 ml of phosphate buffer, pH 6.0, containing sodium perchlorate (0.2 M) were added to the extract before injection into the LC system. The enantiomeric separation of tramadol was achieved using a Chiralcel OD-R column containing cellulose tris-(3,5-dimethylphenylcarbamate) as chiral stationary phase. The mobile phase was a mixture of phosphate buffer, pH 6.0, containing sodium perchlorate (0.2 M) and acetonitrile (75:25). The mobile-phase pH and the NaClO4 concentration were optimized with respect to enantiomeric resolution. The method developed was validated. Recoveries for both enantiomers of tramadol were about 100%. The method was found to be linear in the 2.5-150 ng/ml concentration range [r2=0.999 for (+)- and (-)-tramadol]. The repeatability and intermediate precision at a concentration of 50 ng/ml were 6.5 and 8.7% for (+)-tramadol and 6.1 and 7.6% for (-)-tramadol, respectively. [less ▲]