Quantitative determination of lercanidipine enantiomers in commercial formulations by capillary electrophoresis

Abstract

An enantioselective method based on capillary electrophoresis (CE) using cyclodextrin (CD) as chiral selector was developed and validated for determination of lercanidipine (LER) enantiomers, a drug calcium channel blocker which exerts antihypertensive effects of long duration, in a pharmaceutical formulation. Optimum separation of LER enantiomers was obtained on a 50 cm × 50 μm id capillary using a sodium acetate buffer solution 200 mmol/L pH 4.0 containing 10 mmol/L of 2,3,6-o-methyl-β-cyclodextrin (TM-β-CD) as background electrolyte. The capillary temperature and voltage were 15°C and 25 kV, respectively, hydrodynamic injection and detection at 237 nm. Linearity was obtained in the range 12.5-100 μg/mL for both enantiomers (r ≥ 0.995). The RSD (%) and relative errors (E, %) obtained in precision and accuracy studies (intraday and interday) were lower than 5%. After validation, the method was applied to quantify the enantiomers of LER in commercial tablets and the results were satisfactory in terms of accuracy and precision, both less than 5%. Therefore, this method was found to be appropriate for enantioselective quality control of LER enantiomers in pharmaceutical formulations.

Figure 1

Chemical structure of LER (∗: chiral center).

Figure 2

Effect of (a) TM-β-CD concentration (mmol/L); (b) buffer concentration (mmol/L); (c) temperature (°C) and (d) voltage (kV) on the resolution of LER enantiomers. Experimental conditions: fused-silica uncoated capillary 50 μm id, 60.2 cm in total length and 50.0 cm in effective length, sodium acetate buffer pH 4.0, and 15°C, 25 kV, 237 nm, and injection: 10 seconds (at a pressure of 0.5 psi). Other conditions were changed according to each experiment.

Figure 3

Effect of (a) TM-β-CD concentration (mmol/L); (b) buffer concentration (mmol/L); (c) temperature (°C) and (d) voltage (kV) on the migration time (min) of LER enantiomers. Experimental conditions: fused-silica uncoated capillary 50 μm id, 60.2 cm in total length and 50.0 cm in effective length, sodium acetate buffer pH 4.0, and 15°C, 25 kV, 237 nm, and injection: 10 seconds (at a pressure of 0.5 psi). Other conditions were changed according to each experiment.

Figure 4

Electropherogram of migration order of LER enantiomers. Electrophoretic conditions: fused silica capillary of 50 μm (id), 50 cm effective length, and sodium acetate buffer 200 mmol/L, pH 4.0, TM-β-CD: 10 mmol/L, 15°C, 25 kV.

Figure 5

Typical electropherograms obtained following the analysis of Blank; a standard solution containing racemic LER and commercial tablets. Experimental conditions: fused-silica uncoated capillary 50 μm id and 50.0 cm effective length, +25 kV, 200 mmol/L sodium acetate buffer pH 4.0 (containing 10 mmol/L of TM-β-CD), and 15°C, 237 nm; injection: 10 seconds (at a pressure of 0.5 psi).