Multi-objective optimization strategy based on desirability functions used for electrophoratic separation and quantification of rosiglitazone and glimepiride in plasma and formulations

Drug Test Anal. 2012 Jan;4(1):39-47. doi: 10.1002/dta.260. Epub 2011 Mar 18.


Multiple response simultaneous optimization employing Derringer's desirability function was used for the development of a capillary electrophoresis method for the simultaneous determination of rosiglitazone (RSG) and glimepiride (GLM) in plasma and formulations. Twenty experiments, taking the two resolutions, the analysis time, and the capillary current as the responses with three important factors--buffer morality, volte and column temperature--were used to design mathematical models. The experimental responses were fitted into a second order polynomial and the six responses were simultaneously optimized to predict the optimum conditions for the effective separation of the studied compounds. The separation was carried out by using capillary zone electrophoresis (CZE) with a silica capillary column and diode array detector at 210 nm. The optimum assay conditions were 52 mmol l⁻¹ phosphate buffer, pH 7, and voltage of 22 kV at 29 °C. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The assay limit of detection was 0.02 µg ml⁻¹ and the effective working range at relative standard deviation (RSD) of ≤ 5% was 0.05-16 µg ml⁻¹ (r = 0.999) for both drugs. Analytical recoveries of the studied drugs from spiked plasma were 97.2-101.9 ± 0.31-3.0%. The precision of the assay was satisfactory; RSD was 1.07 and 1.14 for intra- and inter-assay precision, respectively. The proposed method has a great value in routine analysis of RSG and GLM for its therapeutic monitoring and pharmacokinetic studies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Chemistry, Pharmaceutical
  • Drug Monitoring / methods*
  • Drug Monitoring / standards
  • Electrophoresis, Capillary* / standards
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoglycemic Agents / analysis*
  • Hypoglycemic Agents / blood
  • Limit of Detection
  • Models, Chemical
  • Models, Statistical
  • Observer Variation
  • Reproducibility of Results
  • Rosiglitazone
  • Sulfonylurea Compounds / analysis*
  • Sulfonylurea Compounds / blood
  • Tablets
  • Temperature
  • Thiazolidinediones / analysis*
  • Thiazolidinediones / blood


  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Tablets
  • Thiazolidinediones
  • Rosiglitazone
  • glimepiride