[en] 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.
(2000) Eurachem/Citac Guide Quantifying the Uncertainty in Analytical Measurement, , 2nd ed
(2004) EA-4/16, European Co-operation for Accreditation
(1993) Guide to the Expression of Uncertainty in Measurement, , ISO, Geneva
(1995) Analyst, 120, pp. 2303-2308. , Analytical Methods Committee
(1993) International Vocabulary of Basic and General Terms in Metrology, , International Organization for Standardisation 2nd ed. International Organization for Standardisation Geneva
Hund, E., Massart, D.L., Smeyers-Verbeke, J., (2003) Anal. Chim. Acta, 480, pp. 39-52
Marini, R.D., Chiap, P., Boulanger, B., Dewé, W., Hubert, Ph., Crommen, J., (2003) J. Sep. Sci., 26, pp. 536-542
Frishman, H.W., Furberg, D.C., Friedewald, T.W., (1984) N. Eng. J. Med., 310, pp. 830-837
(1984) N. Eng. J. Med., 310, pp. 9-15. , The International Collaborative Study Group
Mazzo, J.D., Loper, E.A., (1987) Anal. Prof. Drug Subst., 16, pp. 641-692
Dickstein, K., Hapnes, R., Aarsland, T., (2001) Am. J. Ophtalmol., 132, pp. 626-631
Boger, W.P., (1979) Drugs, 18, pp. 25-32
(2002) European Pharmacopoeia, 4th Ed., , Addendum. Council of Europe, Strasbourg, France
(1994) Accuracy (Trueness and Precision) of Measurement Methods and Results, , ISO/IEC Standards 5725-2
Mazzo, D.J., (1984) J. Chromatogr., 299, pp. 503-507
Kulkarni, S.P., Amin, P.D., (2000) J. Pharm. Biomed. Anal., 23, pp. 983-987
Vander Heyden, Y., Saevels, J., Roets, E., Hoogmartens, J., Decolin, D., Quaglia, M.G., Van Den Bossche, W., Massart, D.L., (1999) J. Chromatogr. a, 830, pp. 3-28
Dehouck, P., Vander Heyden, Y., Smeyers-Verbeke, J., Massart, D.L., Marini, R.D., Chiap, P., Hubert, Ph., Hoogmartens, J., (2003) J. Chromatogr. a, 1010, pp. 63-74
Grubbs, F.E., (1969) Technometrics, 11, pp. 1-21
Kelly, P.C., (1990) J. Assoc. Off. Anal. Chem., 73, pp. 58-64
Horwitz, W., Kamps, L.R., Boyer, K.W., Quality assurance in the analysis of foods for trace constituents (1980) J. Assoc. Off. Anal. Chem., 63 (6), pp. 1344-1354
Boulanger, B., Chiap, P., Dewe, W., Crommen, J., Hubert, Ph., (2003) J. Pharm. Biomed. Anal., 32, pp. 753-765
Searle, S.R., Casella, G., McCulloch, C.E., (1992) Variance Components, , Wiley New York