Analytical Quality by Design in pharmaceutical quality assurance: Development of a capillary electrophoresis method for the analysis of zolmitriptan and its impurities

Abstract

A fast and selective CE method for the determination of zolmitriptan (ZOL) and its five potential impurities has been developed applying the analytical Quality by Design principles. Voltage, temperature, buffer concentration, and pH were investigated as critical process parameters that can influence the critical quality attributes, represented by critical resolution values between peak pairs, analysis time, and peak efficiency of ZOL-dimer. A symmetric screening matrix was employed for investigating the knowledge space, and a Box-Behnken design was used to evaluate the main, interaction, and quadratic effects of the critical process parameters on the critical quality attributes. Contour plots were drawn highlighting important interactions between buffer concentration and pH, and the gained information was merged into the sweet spot plots. Design space (DS) was established by the combined use of response surface methodology and Monte Carlo simulations, introducing a probability concept and thus allowing the quality of the analytical performances to be assured in a defined domain. The working conditions (with the interval defining the DS) were as follows: BGE, 138 mM (115-150 mM) phosphate buffer pH 2.74 (2.54-2.94); temperature, 25°C (24-25°C); voltage, 30 kV. A control strategy was planned based on method robustness and system suitability criteria. The main advantages of applying the Quality by Design concept consisted of a great increase of knowledge of the analytical system, obtained throughout multivariate techniques, and of the achievement of analytical assurance of quality, derived by probability-based definition of DS. The developed method was finally validated and applied to the analysis of ZOL tablets.

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

“…Most publications are in the form of lectures and posters at industrial scientific meeting series like “CE in the Pharmaceutical and Biotech Industry” and “Analytical Technologies Europe” . The research papers that appeared since the previous review are all by the same group . These papers give excellent explanations on the DoE procedures used.…”

“…Recent publications on the analysis of related substances in pharmaceutical drugs have been compiled in Table . Most separations were carried out in the CZE mode, while four methods applied MEKC and one MEEKC conditions . LODs were in the low microgram per milliliter to sub microgram per milliliter or 0.1% range allowing the sensitive detection of the respective impurities.…”

“…LODs were in the low microgram per milliliter to sub microgram per milliliter or 0.1% range allowing the sensitive detection of the respective impurities. Furthermore, AQbD approaches have been applied in order to develop robust and precise methods for drug purity control . The topic has also been reviewed .…”

A novel quality by design approach for developing an HPLC method to analyze herbal extracts: A case study of sugar content analysis

“…Currently, the concept of quality by design (QbD) has been increasingly applied to the development and optimization of analytical methods, which is known as analytical quality by design (AQbD). Recently, many analytical methods were developed following an AQbD approach, such as the capillary electrophoresis method[ 1 ], Karl Fischer titration methodology[ 2 ], the supercritical fluid chromatography method[ 3 ] and so on. Compared to a traditional analytical method development approach, such as the One-Factor-At-a-time (OFAT) approach[ 4 ], the AQbD approach has several obvious advantages.…”

Development of micellar electrokinetic chromatography method for the determination of three defined impurities in indomethacin

“…Mathematical modeling permits to study the effect of factors on selected responses in more comprehensive way than in univariate approach . DoE is becoming more popular in the CE method development as shown in optimization of BGE composition for the separation of citalopram and its related compounds , development of stereospecific separation of diastereomeric pentapeptide containing methionine sulfoxide , separation of triptans , as well as impurity profiling of zolmitriptan .…”