科研之友
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摘要
A state-of-the-art ultra-performance liquid chromatographic (UPLC) method has been developed for purity testing of carbamazepine. Successful chromatographic separation of the active pharmaceutical ingredient (API) from its impurities was achieved on a WATERS ACQUITY UPLC CSH C18 column with the dimensions 2.1mmx100mm and 1.7 mu m particle size with gradient elution of 0.2% phosphoric acid and acetonitrile in only 5min. Incorporating Quality by Design (QbD) principles to the method development approach by using the statistical software package Fusion AE allows the study of the relationship between chromatographic parameters (factors) and the resolution (response) between the peaks of interest. In a screening phase, the factors known to have a major effect on column selectivity (stationary phase, pH of the aqueous eluent, organic eluent type, gradient time, and slope) were studied. In the second phase, the chromatographic parameters that were identified as affecting the resolution were studied with additional instrument settings. In both phases, statistical concepts with experimental design plans (Design-of-Experiments) are used as an efficient and fast tool to simultaneously gain knowledge regarding the influencing factors and interactions. An operating space within the design space was established and a verification study confirmed the robustness of the final method. Total analysis time was only 5min, which is an impressive 22-fold increase in productivity in comparison to the method published in the European Pharmacopeia.
