Nonaqueous capillary electrophoresis method for the enantiomeric purity determination of S-timolol using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin: validation using the accuracy profile strategy and estimation of uncertainty.

in Journal of Chromatography. A (2006), 1120(1-2), 102-11

Nonaqueous capillary electrophoresis (NACE) was successfully applied to the enantiomeric purity determination of S-timolol maleate using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD ... [more ▼]

Nonaqueous capillary electrophoresis (NACE) was successfully applied to the enantiomeric purity determination of S-timolol maleate using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) as chiral selector. With a background electrolyte made up of a methanolic solution of 0.75 M formic acid, 30 mM potassium camphorsulfonate and containing 30 mM HDMS-beta-CD, the determination of 0.1% of R-timolol in S-timolol could be performed with an enantiomeric resolution of 8.5. Pyridoxine was selected as internal standard. The NACE method was then fully validated by applying a novel strategy using accuracy profiles. It is based on beta-expectation tolerance intervals for the total measurement error which includes trueness and intermediate precision. The uncertainty of measurements derived from beta-expectation tolerance intervals was estimated at each concentration level of the validation standards. To confirm the suitability of the developed and validated method, several real samples of S-timolol maleate containing R-timolol maleate at different concentrations were analysed and the results were compared to those obtained by liquid chromatography. [less ▲]

Applying statistics recomended by regulatory documents.

Conference (2006)

OPTIMIZATION OF MOLECULARLY IMPRINTED SOLID-PHASE EXTRACTION BY MEANS OF EXPERIMENTAL DESIGN PRIOR TO THE DETERMINATION OF METHOTREXATE IN HUMAN PLASMA

Poster (2005, September)

Uncertainty assessment from robustness testing applied on an LC assay for R-timolol and other related substances in S-timolol maleate

in Analytica Chimica Acta (2005), 531(1), 131-140

The robustness testing of a normal-phase liquid chromatographic (LC) method for the determination of R-timolol and other related substances in S-timolol maleate was performed applying a two-level Plackett ... [more ▼]

The robustness testing of a normal-phase liquid chromatographic (LC) method for the determination of R-timolol and other related substances in S-timolol maleate was performed applying a two-level Plackett-Burman design. Two qualitative and five quantitative factors were examined. Two types of responses were considered, qualitative, i.e. chromatographic performance criteria, and quantitative ones. The latter were taken into account to determine if the analytical procedure was robust. The quantitative responses were the contents of R-timolol in two S-timolol maleate samples. Even though some significant factor effects were observed on the qualitative responses, the R-timolol contents were not significantly different from those observed at nominal conditions, which demonstrated the robustness of the procedure. Since the experiments of the Plackett-Burman design can be assimilated to laboratories in an interlaboratory study, uncertainty can be evaluated using the robustness test data. The robustness test was set-up in such a way that the required variances could be estimated. It was shown that the robustness set-up allows estimating the reproducibility uncertainty without performing an interlaboratory study. (c) 2004 Elsevier B.V. All rights reserved. [less ▲]

Recent trends in the validation of bioanalytical methods

Conference (2005)

USE OF THE ACCURACY PROFILE FOR THE VALIDATION OF A DIACETYL-MONOXIME COLORIMETRIC METHOD FOR THE DETERMINATION OF UREA IN TRANSDERMAL IONTOPHORETIC EXTRACTS

Poster (2005)

Collaborative study of an liquid chromatographic method for the determination of R-timolol and other related substances in S-timolol maleate

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 ▲]

Harmonization of strategies for the validation of quantitative analytical procedures - A SFSTP proposal - part I

in Journal of Pharmaceutical & Biomedical Analysis (2004), 36(3), 579-586

This paper is the first part of a summary report of a new commission of the Societe Francaise des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the ... [more ▼]

This paper is the first part of a summary report of a new commission of the Societe Francaise des Sciences et Techniques Pharmaceutiques (SFSTP). The main objective of this commission was the harmonization of approaches for the validation of quantitative analytical procedures. Indeed, the principle of the validation of theses procedures is today widely spread in all the domains of activities where measurements are made. Nevertheless. this simple question of acceptability or not of an analytical procedure for a given application, remains incompletely determined in several cases despite the various regulations relating to the good practices (GLP, GMP,...) and other documents of normative character (ISO, ICH. FDA,...). There are many official documents describing the criteria of validation to be tested, but they do not propose any experimental protocol and limit themselves most often to the general concepts. For those reasons, two previous SFSTP commissions elaborated validation guides to concretely help the industrial scientists in charge of drug development to apply those regulatory recommendations. If these two first guides widely contributed to the use and progress of analytical validations, they present, nevertheless, weaknesses regarding the conclusions of the performed statistical tests and the decisions to be made with respect to the acceptance limits defined by the use of an analytical procedure. The present paper proposes to review even the bases of the analytical validation for developing harmonized approach, by distinguishing notably the diagnosis rules and the decision rules. This latter rule is based on the use of the accuracy profile, uses the notion of total error and allows to simplify the approach of the validation of an analytical procedure while checking the associated risk to its usage. Thanks to this novel validation approach, it is possible to unambiguously demonstrate the fitness for purpose of a new method as stated in all regulatory documents. (C) 2004 Elsevier B.V. All rights reserved. [less ▲]

ENANTIOMERIC PURITY TESTING OF S-KETOPROFEN IN PHARMACEUTICAL FORMULATIONS BY CE USING A DUAL CYCLODEXTRIN SYSTEM

Poster (2004, February)

Setting acceptance criteria and total error criteria

Conference (2004)