ABSTRACT
This study describes a specific, linear, precise, accurate and sensitive method for the determination of a developmental cholesterol-lowering drug formulated in capsules. The method can also determine two known hydrolytic degradants of the drug. Samples are dissolved in acetonitrile-phosphate buffer pH 4.5, diluted with water and assayed by micellar electrokinetic chromatography (MEKC) in a buffer containing 0.1 M borate-0.025 M SDS at 30 degrees C with an applied voltage of 25 kV. Detection is by UV absorbance at 200 nm. The method was cross validated by comparison with a gradient elution HPLC method. The MEKC method gave at least equivalent precision, accuracy and sensitivity to HPLC but was superior in the resolution of the known impurities and gave a considerably shorter analysis time. The method has been accepted as part of a regulatory submission to the US Food and Drug Administration (FDA).
Subject(s)
Anticholesteremic Agents/analysis , Organophosphorus Compounds/analysis , Phenyl Ethers/analysis , Prodrugs/analysis , Sulfonic Acids/analysis , Drug Stability , Electrophoresis, Capillary , Hydrolysis , Reproducibility of ResultsABSTRACT
A micellar electrokinetic chromatography method was optimised for the separation of the six cardiovascular drugs atenolol, nicardipine, nifedipine, diltiazem, verapamil, and amlodipine by investigating the effects of pH, sodium dodecyl sulphate (SDS) concentration, selection and concentration of organic modifier. An electrophoresis buffer of 100 mM borate pH 8.1 containing 50 mM SDS and 15% (v/v) acetone was found to provide the optimum separation with respect to resolution and migration time.
