The successful binomium of multivariate strategies and electrophoresis for the Quality by Design separation of a class of drugs: the case of triptans

Abstract

Quality by Design (QbD) approach was followed having as analytical target profile the determination of different antimigraine drugs (seven triptans, TRP) available on the market. Multivariate strategies were used for defining the design space and solvent-modified MEKC was the selected analytical method. The versatility of electrophoretic technique, allowing a fine modulation of experimental parameters, made it possible to define the design space (DS). The DS limited a suitable range of experimental parameters in which all possible combinations of variables led to an electrokinetic method able to determine all the considered analytes with a predefined quality. Design of experiments and risk analysis fully assisted the method development from the initial investigation of MEKC knowledge space to the DS definition and finally to the control strategy. Applying the working operative conditions, the baseline separation of TRP was obtained in less than 9 min. The method was finally used for the quantification of three TRP in different pharmaceutical products.

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.…”

“…These papers give excellent explanations on the DoE procedures used. Unfortunately, the purposes of the methods in these papers were generally not quantitatively described but subjectively phrased as e.g., “baseline separate and accurately quantitate" . There were no preset, specific numbers given on e.g.…”

Key information related to quality by design (QbD) applications in analytical methods development

“…Pasquini et al [63] used a DoE to optimize the experimental parameters and variables from an electrokinetic method following QbD. From the optimization, a DS was defined, and the developed method was dedicated to quantify three antimigraine drugs in different pharmaceutical products available on the market.…”

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 .…”