|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|146290||2017||25 صفحه PDF||سفارش دهید||5304 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Journal of Pharmaceutical and Biomedical Analysis, Volume 146, 30 November 2017, Pages 402-409
Using a quality by design approach, a capillary electrophoresis method for the simultaneous determination of dextromepromazine and the oxidation product levomepromazine sulfoxide in levomepromazine was developed. The analytical target profile was defined that the method should be able to quantify 0.1% of both impurities with a precision ofâ â¤10%. Hydroxypropyl-Î³-cyclodextrin was used as chiral selector. The critical process parameters cyclodextrin concentration, buffer pH and concentration as well as temperature and applied voltage were studied using a fractional factorial resolution V+ design for defining the knowledge space. A central composite face centered design was used as response surface methodology for deriving the design space by Monte Carlo simulations. The selected working point was a 100Â mM citric acid buffer, pH 2.85, containing 3.6Â mg/mL hydroxypropyl-Î³-cyclodextrin, a temperature of 15Â Â°C and a voltage of 25Â kV. Robustness was estimated using a Plackett-Burman design. The method was subsequently validated in the relative concentration range of 0.1%â1.0% of the impurities for a solution containing 0.25Â mg/mL levomepromazine. The method was applied to the determination of the purity of the reference substance of the European Pharmacopoeia and of the drug in a commercial injection solution.