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 ▲]

Validation des méthodes d’analyse des médicaments dans les milieux biologiques

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

Méthodes chromatographiques de dosage dans les milieux biologiques : exemple d'application de la stratégie de validation - Rapport d'une commission SFSTP

in STP Pharma Pratiques (1998), 8(2), 81-107

Validation des méthodes d’analyse des médicaments dans les milieux biologiques

Conference (1997)

Selecting Derringer’s desirability functions that guarantee Pareto optimality : an application to the optimization of a liquid chromatography separation

Poster (1997)

On-line combination of dialysis with trace enrichment on a cation-exchange precolumn for the automated LC determination of sotalol in plasma

Poster (1997)

SFSTP guide on validation of bioanalytical methods : a proposal

Conference (1996)

Variabilité comportementale et conditionnement operant chez l'animal: Revue critique

in Année Psychologique (L') (1987), 87

Le but de cette revue, qui dresse un bilan des connaissances relatives à la variabilité comportementale en conditionnement opérant chez l'animal, est d'ouvrir la voie aux recherches futures. Les ... [more ▼]

Le but de cette revue, qui dresse un bilan des connaissances relatives à la variabilité comportementale en conditionnement opérant chez l'animal, est d'ouvrir la voie aux recherches futures. Les recherches présentées sont organisées autour de deux axes: 1) L'examen de la variabilité spontanée de la réponse opérante en fonction de divers facteurs; et, 2) L'étude des possibilités de renforcement sélectif des variations de la réponse opérante - variabilité requise. A l'issue de cette revue, il apparaît clairement que les mécanismes de variation ont été beaucoup moins étudiés que les mécanismes de sélection du comportement (mécanismes pourtant complémentaires en théorie de l'apprentissage). Quelques résultats laissent entrevoir la possibilité de considérer la variabilité comportementale comme une dimension inhérente au comportement, sensible aux contingences de renforcement, comme le sont la force, la durée... [less ▲]