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

摘要

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 x 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 (γ~2 >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 ug mL~(-1) and 0.5 ug mL~(-1) for nitrendipine and atenolol and the limits of quantification of this method were 2.5 ug 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.