Capillary electrophoresis assay method for metoprolol and hydrochlorothiazide in their combined dosage form with multivariate optimization.

The current manuscript reports the first capillary electrophoresis method for the separation and quantification of metoprolol (MET) and hydrochlorothiazide (HCT) in their combined dosage form. MET and HCT were detected at 240 and 214 nm, respectively, using a photodiode array detector. The univariate approach was used for optimizing voltage, injection time and capillary temperature. The factorial design with response surface plots, as a multivariate approach, was used to study the effect of buffer concentration and pH on resolution, peak area and migration time. The optimum conditions were 50 mmol/L phosphate at pH 9.5, injection time 10.0 s, voltage 25 kV and capillary temperature 25°C. The method was linear in the range of 2.5-250 µg/mL for both drugs with correlation coefficients above 0.9997. Additionally, acceptable recovery of the contents of MET and HCT in their formulations (96.0-100.3%) with acceptable precision (1.38-2.60 %) were achieved. Moreover, the limits of detection of MET and HCT were 0.02 and 0.01 µg/mL, respectively, which were suitable for pharmaceutical analysis.