Optimization and validation of a MEKC method assisted by Box–Behnken Design for fast and simultaneous determination of nitrendipine and atenolol in new antihypertensive combination tablets

Abstract

In this paper, we established a micellar electrokinetic chromatography method for fast and simultaneous determination of nitrendipine and atenolol in new antihypertensive combination tablets. Buffer conditions were optimized by using a multivariate response surface methodology (RSM) established by Box–Behnken Design in terms of sodium dodecyl sulfate concentration, buffer concentration and pH of buffer. Under the optimum buffer conditions, the separation of the two drugs can be finished in 3 minutes in a 31.2 cm × 50 μm fused-silica capillary at an applied voltage of 25 kV and the temperature of 25 °C. The optimal running buffer (pH 8.9) was Na₂B₄O₇ (7.5 mmol L⁻¹) and NaH₂PO₄ (30 mmol L⁻¹) containing 15 mmol L⁻¹ sodium dodecyl sulfate. Good correlation coefficients were found (γ² >0.999) at concentrations of 5–17.5 μg mL⁻¹ for nitrendipine and 10–35 μg mL⁻¹ for atenolol, respectively. All the RSD results of precision experiments were below 3%. The recoveries of nitrendipine and atenolol were 98.98–100.15% and 99.46–101.18%, respectively. The limits of detection of this method were 1 μg mL⁻¹ and 0.5 μg mL⁻¹ for nitrendipine and atenolol and the limits of quantification of this method were 2.5 μg mL⁻¹ for nitrendipine and 1.5 μg mL⁻¹ for atenolol. After the optimization, the method was successfully applied for the content uniformity test according to the United States Pharmacopeia.