Nonaqueous capillary electrophoresis method for the enantiomeric purity determination of S-timolol using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin: validation using the accuracy profile strategy and estimation of uncertainty.
Nonaqueous capillary electrophoresis (NACE) was successfully applied to the enantiomeric purity determination of S-timolol maleate using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) as chiral selector. With a background electrolyte made up of a methanolic solution of 0.75 M formic acid, 30 mM potassium camphorsulfonate and containing 30 mM HDMS-beta-CD, the determination of 0.1% of R-timolol in S-timolol could be performed with an enantiomeric resolution of 8.5. Pyridoxine was selected as internal standard. The NACE method was then fully validated by applying a novel strategy using accuracy profiles. It is based on beta-expectation tolerance intervals for the total measurement error which includes trueness and intermediate precision. The uncertainty of measurements derived from beta-expectation tolerance intervals was estimated at each concentration level of the validation standards. To confirm the suitability of the developed and validated method, several real samples of S-timolol maleate containing R-timolol maleate at different concentrations were analysed and the results were compared to those obtained by liquid chromatography.
Marini
Roland Djang'eing'a
RD
Laboratory of Analytical Chemistry, Bioanalytical Chemistry Research Unit, Institute of Pharmacy, University of Liège, CHU, B36, B-4000 Liège 1, Belgium.
Servais
Anne-Catherine
AC
Rozet
Eric
E
Chiap
Patrice
P
Boulanger
Bruno
B
Rudaz
Serge
S
Crommen
Jacques
J
Hubert
Philippe
P
Fillet
Marianne
M
D000959:Antihypertensive Agents / Q000737:chemistry / Q000302:isolation & purification; D019075:Electrophoresis, Capillary / Q000379:methods*; D015394:Molecular Structure; D012015:Reference Standards; D012044:Regression Analysis; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013999:Timolol / Q000737:chemistry / Q000302:isolation & purification*; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000592:standards
D000959:Antihypertensive Agents; D047392:beta-Cyclodextrins; C400661:heptakis(2,3-dimethyl-6-sulfato)cyclodextrin; D013999:Timolol