title: Interlaboratory study of a NACE method for the determination of R-timolol content in S-timolol maleate: assessment of uncertainty.
abstract: 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.
authors.affiliation: Laboratory of Analytical Chemistry, Institute of Pharmacy, University of Liège, Liège, Belgium.
authors.forename: Roland Djang'eing'a
authors.initials: RD
authors.lastname: Marini
authors.forename: Carl
authors.initials: C
authors.lastname: Groom
authors.forename: François R
authors.initials: FR
authors.lastname: Doucet
authors.forename: Jalal
authors.initials: J
authors.lastname: Hawari
authors.forename: Yaser
authors.initials: Y
authors.lastname: Bitar
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
authors.forename: Roberto
authors.initials: R
authors.lastname: Gotti
authors.forename: Julie
authors.initials: J
authors.lastname: Schappler
authors.forename: Serge
authors.initials: S
authors.lastname: Rudaz
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.forename: Roelof
authors.initials: R
authors.lastname: Mol
authors.forename: Govert W
authors.initials: GW
authors.lastname: Somsen
authors.forename: Gerhardus J
authors.initials: GJ
authors.lastname: de Jong
authors.forename: Pham Thi Thanh
authors.initials: PT
authors.lastname: Ha
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Ann
authors.initials: A
authors.lastname: Van Schepdael
authors.forename: Jos
authors.initials: J
authors.lastname: Hoogmartens
authors.forename: Willy
authors.initials: W
authors.lastname: Briône
authors.forename: Attilio
authors.initials: A
authors.lastname: Ceccato
authors.forename: Bruno
authors.initials: B
authors.lastname: Boulanger
authors.forename: Debby
authors.initials: D
authors.lastname: Mangelings
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vander Heyden
authors.forename: Willy
authors.initials: W
authors.lastname: Van Ael
authors.forename: Ilias
authors.initials: I
authors.lastname: Jimidar
authors.forename: Matteo
authors.initials: M
authors.lastname: Pedrini
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Servais
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
authors.forename: Jacques
authors.initials: J
authors.lastname: Crommen
authors.forename: Eric
authors.initials: E
authors.lastname: Rozet
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis*; D004340:Drug Contamination; D019075:Electrophoresis, Capillary / Q000379:methods*; D015203:Reproducibility of Results; D018581:Technology Transfer; D013999:Timolol / Q000032:analysis*; D035501:Uncertainty
chemical_list: D000319:Adrenergic beta-Antagonists; D013999:Timolol