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