Robustness testing of a chiral NACE method for R-timolol determination in S-timolol maleate and uncertainty assessment from quantitative data.
A robustness test of a capillary electrophoresis method for the chiral separation of timolol in nonaqueous acidified media was performed. A two-level Plackett-Burman design was applied in which one qualitative and six quantitative factors were examined. Resolution, migration times and relative migration times to pyridoxine (selected as internal standard) were examined as qualitative responses to evaluate electrophoretic performance. A quantitative response, the content of R-timolol in S-timolol maleate sample, was also considered. Even though some significant factor effects were observed on the qualitative responses, it was still possible to quantify the R-timolol in the S-timolol maleate samples properly. The quantitative response was not significantly affected by the selected factors, demonstrating the robustness of the procedure. However, the use of different HDMS-beta-CD batches seemed to affect both types of responses necessitating to introduce a warning in 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.
Marini
R D
RD
Laboratory of Analytical Chemistry, Institute of Pharmacy, University of Liège, CHU, B36, B-4000 Liege 1, Belgium.
Rozet
E
E
Vander Heyden
Y
Y
Ziemons
E
E
Boulanger
B
B
Bouklouze
A
A
Servais
A-C
AC
Fillet
M
M
Crommen
J
J
Hubert
Ph
P
D000319:Adrenergic beta-Antagonists / Q000032:analysis*; D004340:Drug Contamination; D019075:Electrophoresis, Capillary / Q000379:methods*; D012015:Reference Standards; D015203:Reproducibility of Results; D013237:Stereoisomerism; D018581:Technology Transfer; D013999:Timolol / Q000032:analysis*; D035501:Uncertainty
D000319:Adrenergic beta-Antagonists; D013999:Timolol