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Collaborative study of an liquid chromatographic method for the determination of R-timolol and other related substances in S-timolol maleate |
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| Authors: | R.D. Marini,N. Matthijs,J. Smeyers-Verbeke,J. Hoogmartens,A. Ceccato,Ph. Goedert,C. Herbots,R. Herrá ez-Herná ndez,P. Campí ns-falcó ,J. De Beer,P. Chiap,Ph. Hubert |
| Affiliation: | a Laboratory of Analytical Chemistry, Institute of Pharmacy, University of Liège, CHU, B36, B-4000 Liege 1, Belgium b Pharmaceutical and Biomedical Analysis, VUB, Brussels, Belgium c Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, K.U.L, Leuven, Belgium d Galephar M/F, Marche-En-Famenne, Belgium e Association Pharmaceutique Belge, Service de Contrôle des Médicaments, Brussels, Belgium f Lilly Development Centre, Biopharmaceutics and Drug Delivery, Mont-Saint-Guibert, Belgium g Departamento de Química Analítica, Facultad de Química, Burjassot, Spain h Scientific Institute of Health, Brussels, Belgium i Lilly Development Centre, Statistical & Mathematical Sciences, Mont-Saint-Guibert, Belgium j Department of Analytical Pharmaceutical Chemistry, Institute of Pharmacy, University of Liège, Belgium |
| Abstract: | 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 ( ), the between-days ( ) and the between-replicates ( ). The variances of repeatability ( ) and reproducibility ( ) were then calculated using the equations  and  . 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. |
| Keywords: | Collaborative study Uncertainty estimation Reproducibility R-timolol Degradation products Liquid chromatography |
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