title: 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.
abstract: 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.
authors.affiliation: Laboratory of Analytical Chemistry, Bioanalytical Chemistry Research Unit, Institute of Pharmacy, University of Liège, CHU, B36, B-4000 Liège 1, Belgium.
authors.forename: Roland Djang'eing'a
authors.initials: RD
authors.lastname: Marini
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Servais
authors.forename: Eric
authors.initials: E
authors.lastname: Rozet
authors.forename: Patrice
authors.initials: P
authors.lastname: Chiap
authors.forename: Bruno
authors.initials: B
authors.lastname: Boulanger
authors.forename: Serge
authors.initials: S
authors.lastname: Rudaz
authors.forename: Jacques
authors.initials: J
authors.lastname: Crommen
authors.forename: Philippe
authors.initials: P
authors.lastname: Hubert
authors.forename: Marianne
authors.initials: M
authors.lastname: Fillet
mesh_terms: 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
chemical_list: D000959:Antihypertensive Agents; D047392:beta-Cyclodextrins; C400661:heptakis(2,3-dimethyl-6-sulfato)cyclodextrin; D013999:Timolol