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

J Chromatogr A. 2006 Jul 7;1120(1-2):102-11. doi: 10.1016/j.chroma.2006.03.104. Epub 2006 Apr 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / chemistry
  • Antihypertensive Agents / isolation & purification
  • Electrophoresis, Capillary / methods*
  • Molecular Structure
  • Reference Standards
  • Regression Analysis
  • Reproducibility of Results
  • Stereoisomerism
  • Timolol / chemistry
  • Timolol / isolation & purification*
  • beta-Cyclodextrins / chemistry*
  • beta-Cyclodextrins / standards

Substances

  • Antihypertensive Agents
  • beta-Cyclodextrins
  • heptakis(2,3-dimethyl-6-sulfato)cyclodextrin
  • Timolol