Biomedical subjects

Y Vander Heyden

Publications and source records attributed to Y Vander Heyden.

60 records · Page 4Linked to original sources

PubMed2000

Robustness testing of a reversed-phase high-performance liquid chromatographic assay: comparison of fractional and asymmetrical factorial designs.

Robustness tests were performed on a reversed-phase HPLC assay for triadimenol. Different experimental designs were compared. Two-level fractional factorial designs with different resolutions were used to study the influence of procedure-related factors. The factors chromatographic column manufacturer at four levels and instrument at three levels were stepwise included in the study using asymmetrical factorial designs. The significance of the factor effects was determined statistically, using two types of error estimates in the calculation of critical effects, and graphically, by means of half-normal plots. The asymmetrical designs turned out to be an efficient and economic method to examine the influence of factors at different numbers of levels in the robustness testing of analytical methods.

Chromatography, High Pressure Liquid↗

PubMed1999

Rapid development of the enantiomeric separation of beta-blockers by capillary electrophoresis using an experimental design approach.

A rapid method for determining the separation conditions for chiral resolution of eleven beta-blocking drug substances by capillary electrophoresis is described, using an experimental design approach. An acidic phosphate-triethanolamine buffer and an uncoated fused-silica capillary were used for all experiments. Several modified cyclodextrins were applied as chiral selectors: sulfobutyl ether beta-cyclodextrin (SBE-beta CD), dimethyl beta-cyclodextrin (DM-beta CD), carboxymethyl beta-cyclodextrin (CM-beta CD), and hydroxypropyl beta-cyclodextrin (HP-beta CD). Two different fractional factorial experimental designs were applied: (1) a design examining four factors at three levels (3(4-2)) and (2) one examining three factors at two levels (2(3-1)). The factors studied were: type of cyclodextrin, cyclodextrin concentration, pH of the background electrolyte and percentage of organic modifier. Enough resolution for the separation of the enantiomers and even for their quantification was reached. The same scheme is proposed when a fast chiral separation method needs to be developed for other drug families.

Adrenergic beta-Antagonists↗

PubMed1999

Nested designs in ruggedness testing.

Nested designs were performed in order to execute a ruggedness test according to the United States Pharmacopeia definition for ruggedness, in which mainly non-procedure related factors are examined. Several nested designs have been executed on a high performance liquid chromatography assay to determine tetracycline and related substances in bulk samples of tetracycline. Factors such as different laboratories, analysts, instruments, columns, days and batches were examined. The interpretation methods described in the literature were found to cause problems. In these methods the variances of the examined factors are estimated from the calculated mean square values and from the equation for the expected mean squares. Very frequently, negative variance estimates were obtained. Their absolute values were found to be dependent on the influence of the factor examined below it in the design, on the examined response. Therefore an alternative interpretation method for nested designs, based on pooled variances, was proposed and found to be appropriate to use for ruggedness testing purposes. Both approaches, the one from the literature and the one proposed here, were tested on simulated data coming from a nested design with four factors and on the experimentally measured data.

Analysis of Variance↗

PubMed1999

Use of experimental design to optimise a flow injection analysis assay for L-N-monomethylarginine.

A flow injection analysis (FIA) method to determine L-N-monomethylarginine, based on the reaction with ortho-phthalaldehyde in the presence of a suitable thiol-group, was optimised using experimental design. Two different approaches were followed wherein, (i) critical factors were identified in a screening design, and (ii) the simplex algorithm was used for further optimisation. In the first approach, the chemical reaction was optimised off-line and the optimal chemical conditions were transferred to the FIA-system. In the second approach the reaction and the FIA-system parameters were optimised together. The on-line approach is preferred.

Acetylcysteine↗

PubMed1998

RTS, a computer program for the experimental set-up and interpretation of ruggedness tests.

A computer program is described for the experimental set-up and interpretation of ruggedness tests. The implemented strategy was based on a number of case studies and contains both recommended designs and minimal designs. The minimal designs reduce the number of experiments, but they cannot be statistically interpreted based on the interaction or dummy factor effects. The use of randomization tests as an alternative statistical interpretation method for the significance of the effects was examined. Some of the minimal designs are expandable to designs with characteristics similar to those of the recommended designs. The program is designed to facilitate the selection of the designs and the interpretation of the results and to prevent or detect problems such as drifting of responses.

Chemistry Techniques, Analytical↗

PubMed1998

Ruggedness testing of chromatographic methods: selection of factors and levels.

The first step in a ruggedness test is the selection of factors to be examined and their levels. In this paper, both topics are discussed, thereby completing a strategy described earlier. It is demonstrated, by means of some examples, that depending on the formulation (definition) of a factor, information that is physically more or less meaningful is extracted from the experimental design results. Among others, the inclusion of the compounds of a buffer and of the components of a mixture in a screening design were examined. A general guideline to select the levels of the factors in a ruggedness test was proposed. Some special cases, i.e. asymmetric intervals around the nominal level, were also discussed.

Chemistry Techniques, Analytical↗