References of "Ceccato, Attilio"
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See detailDevelopment of a new predictive modelling technique to find with confidence equivalence zone and design space of chromatographic analytical methods
Lebrun, Pierre ULg; Govaerts, Bernadette; Debrus, Benjamin ULg et al

in Chemometrics and Intelligent Laboratory Systems (2008), 91

A new method for modelling chromatographic responses is presented as a critical piece for the achievement of automated development of analytical methods. This methodology is based on four parts. First, we ... [more ▼]

A new method for modelling chromatographic responses is presented as a critical piece for the achievement of automated development of analytical methods. This methodology is based on four parts. First, we propose to use a very little set of statistical equations to create predictive models for retention time based responses as the apex, the width and the asymmetry of peaks. Second, an experimental design is set up to realize experiments. Third, using grid search over the domain, multi criteria decision is taken with respect to different local or global optimization criteria, used as desirability functions. This allows finding an optimal chromatogram. Fourth, we advice to investigate how the predictive error of the models propagates around optimal solution. This allows to give confidence in the optimal solution, in finding a set of zones that presumably will give an acceptable solution. Design spaces can be derived with a similar technique. The approach is exemplified with a real case and predictions of models at optimal analytical conditions are validated through new experiments. Flexibility is left over all the presented methodology. [less ▲]

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See detailUsing tolerance intervals in pre-study validation of analytical methods to predict in-study results - The fit-for-future-purpose concept
Rozet, Eric ULg; Hubert, Cédric ULg; Ceccato, Attilio ULg et al

in Journal of Chromatography. A (2007), 1158(1-2), 126-137

It is recognized that the purpose of validation of analytical methods is to demonstrate that the method is suited for its intended purpose. Validation is not only required by regulatory authorities, but ... [more ▼]

It is recognized that the purpose of validation of analytical methods is to demonstrate that the method is suited for its intended purpose. Validation is not only required by regulatory authorities, but is also a decisive phase before the routine use of the method. For a quantitative analytical method the objective is to quantify the target analytes with a known and suitable accuracy. For that purpose, first, a decision about the validity of the method based on prediction is proposed: a method is declared proper for routine application if it is considered that most of the future results generated will be accurate enough. This can be achieved by using the "beta-expectation tolerance interval" (accuracy profile) as the decision tool to assess the validity of the analytical method. Moreover, the concept of "fit-for-purpose" is also proposed here to select the most relevant response function as calibration curve, i.e. choosing a response function based solely on the predicted results this model will allow to obtain. This paper reports four case studies where the results obtained with quality control samples in routine were compared to predictions made in the validation phase. Predictions made using the "beta-expectation tolerance interval" are shown to be accurate and trustful for decision making. It is therefore suggested that an adequate way to conciliate both the objectives of the analytical method in routine analysis and those of the validation step consists in taking the decision about the validity of the analytical method based on prediction of the future results using the most appropriate response function curve, i.e. the fit-for-future-purpose concept. [less ▲]

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See detailAnalysis of recent pharmaceutical regulatory documents on analytical method validation.
Rozet, Eric ULg; Ceccato, Attilio ULg; Hubert, Cédric ULg et al

in Journal of Chromatography. A (2007), 1158(1-2), 111-25

All analysts face the same situations as method validation is the process of proving that an analytical method is acceptable for its intended purpose. In order to resolve this problem, the analyst refers ... [more ▼]

All analysts face the same situations as method validation is the process of proving that an analytical method is acceptable for its intended purpose. In order to resolve this problem, the analyst refers to regulatory or guidance documents, and therefore the validity of the analytical methods is dependent on the guidance, terminology and methodology, proposed in these documents. It is therefore of prime importance to have clear definitions of the different validation criteria used to assess this validity. It is also necessary to have methodologies in accordance with these definitions and consequently to use statistical methods which are relevant with these definitions, the objective of the validation and the objective of the analytical method. The main purpose of this paper is to outline the inconsistencies between some definitions of the criteria and the experimental procedures proposed to evaluate those criteria in recent documents dedicated to the validation of analytical methods in the pharmaceutical field, together with the risks and problems when trying to cope with contradictory, and sometimes scientifically irrelevant, requirements and definitions. [less ▲]

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See detailEvaluation of Analytical Method Transfer on a Risk Based Methodology using Total Error
Rozet, Eric ULg; Dewe, W.; Govaerts, B. et al

Conference (2007)

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See detailThe transfer of a LC-UV method for the determination of fenofibrate and fenofibric acid in Lidoses: Use of total error as decision criterion
Rozet, Eric ULg; Mertens, Bénédicte; Dewé, Walthère ULg et al

in Journal of Pharmaceutical & Biomedical Analysis (2006), 42(1), 64-70

Two new statistical approaches to assess the validity of the transfer of a LC-UV method for the determination of fenofibrate and fenofibric acid were investigated and compared to the conventional ... [more ▼]

Two new statistical approaches to assess the validity of the transfer of a LC-UV method for the determination of fenofibrate and fenofibric acid were investigated and compared to the conventional approaches generally used in this domain. These new approaches, namely the Tolerance Interval and the Risk approaches, are based on the simultaneous evaluation of the systematic (or trueness) and random (or precision) errors of the transfer into a single criterion called total error (or accuracy). The results of the transfer showed that only the total error based approaches fulfilled the objective of an analytical method transfer, i.e. to give guarantees that each future measurement made by the receiving laboratory will be close enough to the true value of the analyte in the sample. Furthermore the Risk approach was the most powerful one and allowed the estimation of the risk to have future measurements out of specification in the receiving laboratory, therefore being a risk management tool. (c) 2006 Elsevier B.V. All rights reserved. [less ▲]

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See detailInterlaboratory study of a NACE method for the determination of R-timolol content in S-timolol maleate: assessment of uncertainty.
Marini Djang'Eing'A, Roland ULg; Groom, Carl; Doucet, Francois R et al

in Electrophoresis (2006), 27(12), 2386-99

Analyses of statistical variance were applied to evaluate the precision and practicality of a CD-based NACE assay for R-timolol after enantiomeric separation of R- and S-timolol. Data were collected in an ... [more ▼]

Analyses of statistical variance were applied to evaluate the precision and practicality of a CD-based NACE assay for R-timolol after enantiomeric separation of R- and S-timolol. Data were collected in an interlaboratory study by 11 participating laboratories located in Europe and North America. General qualitative method performance was examined using suitability descriptors (i.e. resolution, selectivity, migration times and S/N), while precision was determined by quantification of variances in the determination of R-timolol at four different impurity levels in S-timolol maleate samples. The interlaboratory trials were designed in accordance with the ISO guideline 5725-2. This allowed estimating for each sample, the different variances, i.e. between-laboratory (s2(Laboratories)), between-day (s2(Days)) and between-replicate (s2(Replicates)). The variances of repeatability (s2r) and reproducibility (s2R) were then calculated. The estimated uncertainty, derived from the precision estimates, seems to be concentration-dependent above a given threshold. This example of R-timolol illustrates how a laboratory can evaluate uncertainty in general. [less ▲]

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See detailCollaborative study of an liquid chromatographic method for the determination of R-timolol and other related substances in S-timolol maleate
Marini, R. D.; Matthijs, N.; Vanderheyden, Yvan et al

in Analytica Chimica Acta (2005), 546(2), 182-192

A collaborative study applying an enantiomeric liquid chromatographic (LC) method was carried out to determine the content of the enantiomeric impurity R-timolol and other related substances in three ... [more ▼]

A collaborative study applying an enantiomeric liquid chromatographic (LC) method was carried out to determine the content of the enantiomeric impurity R-timolol and other related substances in three different S-timolol maleate samples. Eight laboratories, all located in Europe, participated in the study. The quantitative results obtained were used to estimate the uncertainty on the content of the different impurities. For that purpose, a set-up was adapted from the ISO guidelines 5725-2, which allowed the estimation of the different variances, i.e. the between-laboratories (s(laboratories)(2)), the between-days (s(days)(2)) and the between-replicates (s(replicates)(2)), The variances of repeatability (s(r)(2)) and reproducibility (s(R)(2)) were then calculated using the equations s(r)(2) = s(replicates)(2) and s(R)(2) = s(replicates)(2) + s(days)(2) + s(laboratories)(2). For the timolol impurities, it was found that the estimated uncertainty seem to be concentration-dependent. Since the LC method which combines the compendial ones for enantiomeric purity and related substances testing was applied to evaluate uncertainty in this collaborative study, it was shown how a laboratory can evaluate the uncertainty of its results when applying the method in the future. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

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See detailValidation of a liquid chromatographic-tandem mass spectrometric method for the determination of loperamide in human plasma
Streel, B.; Ceccato, Attilio ULg; Klinkenberg, R. et al

in Journal of Chromatography. B : Analytical Technologies in the Biomedical & Life Sciences (2005), 814(2), 263-273

A sensitive and selective method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the quantitative determination of loperamide in human plasma. Automated solid ... [more ▼]

A sensitive and selective method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the quantitative determination of loperamide in human plasma. Automated solid-phase extraction (SPE) on disposable extraction cartridges (DEC) is used to isolate the compounds from the biological matrix and to prepare a cleaner sample before injection and analysis in the LC-MS/MS system. After conditioning, the plasma sample is loaded on the DEC filled with endcapped ethyl silica (C2(EC)) and washed twice with water. The analytes are therefore eluted by dispensing methanol. The eluate is then collected and added with ammonium acetate solution in order to inject an aliquot of this final extract in the LC-MS/MS system. On-line LC-MS/MS system using atmospheric pressure chemical ionization (APCI) has been developed for the determination of loperamide. The separation is obtained on a octadecylsilica based stationary phase using a mobile phase consisting in a mixture of methanol and 5 mM ammonium acetate solution (25:75, v/v). Clonazepam is used as internal standard (IS). The MS/MS ion transitions monitored are m/z 477 --> 266 and 316 --> 270 for loperamide and clonazepam, respectively. The most appropriate regression model of the response function as well as the limit of quantitation were first selected during the pre-validation step. These latter criteria were then assessed during the formal validation step. The limit of quantitation (LOQ) was around 50 pg/ml for loperamide. The method was also validated with respect to recovery, precision, trueness, accuracy and linearity. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

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See detailCollaborative study of an liquid chromatographic method for the determination of R-timolol and other related substances in S-timolol maleate
Marini Djang'Eing'A, Roland ULg; Matthijs, N.; Heyden, Y. V. et al

in Analytica Chimica Acta (2005), 546(2), 182-192

A collaborative study applying an enantiomeric liquid chromatographic (LC) method was carried out to determine the content of the enantiomeric impurity R-timolol and other related substances in three ... [more ▼]

A collaborative study applying an enantiomeric liquid chromatographic (LC) method was carried out to determine the content of the enantiomeric impurity R-timolol and other related substances in three different S-timolol maleate samples. Eight laboratories, all located in Europe, participated in the study. The quantitative results obtained were used to estimate the uncertainty on the content of the different impurities. For that purpose, a set-up was adapted from the ISO guidelines 5725-2, which allowed the estimation of the different variances, i.e. the between-laboratories (s(laboratories)(2)), the between-days (s(days)(2)) and the between-replicates (s(replicates)(2)), The variances of repeatability (s(r)(2)) and reproducibility (s(R)(2)) were then calculated using the equations s(r)(2) = s(replicates)(2) and s(R)(2) = s(replicates)(2) + s(days)(2) + s(laboratories)(2). For the timolol impurities, it was found that the estimated uncertainty seem to be concentration-dependent. Since the LC method which combines the compendial ones for enantiomeric purity and related substances testing was applied to evaluate uncertainty in this collaborative study, it was shown how a laboratory can evaluate the uncertainty of its results when applying the method in the future. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

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See detailFully automated method for the liquid chromatographic-tandem mass spectrometric determination of cyproterone acetate in human plasma using restricted access material for on-line sample clean-up
Christiaens, B.; Fillet, Marianne ULg; Chiap, Patrice ULg et al

in Journal of Chromatography. A (2004), 1056(1-2), 105-110

A new automated method for the quantitative analysis of cyproterone acetate (CPA) in human plasma has been developed using on-line solid phase extraction (SPE) prior to the LC-MS/MS determination. The ... [more ▼]

A new automated method for the quantitative analysis of cyproterone acetate (CPA) in human plasma has been developed using on-line solid phase extraction (SPE) prior to the LC-MS/MS determination. The method was based on the use of a pre-column packed with internal-surface reversed-phase material (LiChrospher RP-4 ADS, 25 mm x 2 mm) for sample clean-up coupled to LC separation on an octadecyl silica stationary phase by means of a column switching system. A 30 microl plasma sample volume was injected directly onto the pre-column using a mixture of water, acetonitrile and formic acid (90:10:0.1 (v/v/v)) adjusted to pH 4.0 with diluted ammonia as washing liquid. The analyte was then eluted in the back-flush mode with the LC mobile phase consisting of water, methanol and formic acid (10:90:0.1 (v/v/v)). The dispensing flow rates of the washing liquid and the LC mobile phase were 300 microl min(-1). Medroxyprogesterone acetate (MPA) was used as internal standard. The MS ionization of the analytes was achieved using electrospray (ESI) in the positive ion mode. The pseudomolecular ionic species of CPA and MPA (417.4 and 387.5) were selected to generate daughter ions at 357.4 and 327.5, respectively. Finally, the developed method was validated according to a new approach using accuracy profiles as a decision tool. Very good results with respect to accuracy, detectability, repeatability, intermediate precision and selectivity were obtained. The LOQ of cyproterone acetate was 300 pg ml(-1). [less ▲]

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See detailFully automated method for the liquid chromatographic-tandem mass spectrometric determination of cyproterone acetate in human plasma using restricted access material for on-line sample clean-up.
Christians, Benoit; Fillet, Marianne ULg; Chiap, Patrice ULg et al

in Journal of Chromatography. A (2004), 1056(1-2), 105-10

A new automated method for the quantitative analysis of cyproterone acetate (CPA) in human plasma has been developed using on-line solid phase extraction (SPE) prior to the LC-MS/MS determination. The ... [more ▼]

A new automated method for the quantitative analysis of cyproterone acetate (CPA) in human plasma has been developed using on-line solid phase extraction (SPE) prior to the LC-MS/MS determination. The method was based on the use of a pre-column packed with internal-surface reversed-phase material (LiChrospher RP-4 ADS, 25 mm x 2 mm) for sample clean-up coupled to LC separation on an octadecyl silica stationary phase by means of a column switching system. A 30 microl plasma sample volume was injected directly onto the pre-column using a mixture of water, acetonitrile and formic acid (90:10:0.1 (v/v/v)) adjusted to pH 4.0 with diluted ammonia as washing liquid. The analyte was then eluted in the back-flush mode with the LC mobile phase consisting of water, methanol and formic acid (10:90:0.1 (v/v/v)). The dispensing flow rates of the washing liquid and the LC mobile phase were 300 microl min(-1). Medroxyprogesterone acetate (MPA) was used as internal standard. The MS ionization of the analytes was achieved using electrospray (ESI) in the positive ion mode. The pseudomolecular ionic species of CPA and MPA (417.4 and 387.5) were selected to generate daughter ions at 357.4 and 327.5, respectively. Finally, the developed method was validated according to a new approach using accuracy profiles as a decision tool. Very good results with respect to accuracy, detectability, repeatability, intermediate precision and selectivity were obtained. The LOQ of cyproterone acetate was 300 pg ml(-1). [less ▲]

Detailed reference viewed: 40 (1 ULg)