Micellar electrokinetic chromatography stability indicating assay and content uniformity determination for a cholesterol-lowering drug product.
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).
Bretnall
A E
AE
Bristol-Myers Squibb, Pharmaceutical Research Institute, Moreton, Merseyside, UK.
Hodgkinson
M M
MM
Clarke
G S
GS
D000924:Anticholesteremic Agents / Q000032:analysis*; D004355:Drug Stability; D019075:Electrophoresis, Capillary; D006868:Hydrolysis; D009943:Organophosphorus Compounds / Q000032:analysis*; D010647:Phenyl Ethers / Q000032:analysis*; D011355:Prodrugs / Q000032:analysis*; D015203:Reproducibility of Results; D013451:Sulfonic Acids / Q000032:analysis*
D000924:Anticholesteremic Agents; C107094:BMS 187745; C103127:BMS 188494-04; C107322:BMS 196716; D009943:Organophosphorus Compounds; D010647:Phenyl Ethers; D011355:Prodrugs; D013451:Sulfonic Acids