Quality by design‐guided development of a capillary electrophoresis method for the simultaneous chiral purity determination and impurity profiling of tamsulosin

Abstract

Analytical Quality by Design principles using the design of experiments were applied for the development of a capillary electrophoresis method for the determination of enantiomeric purity and chemically related impurities of tamsulosin. From initial scouting experiments, a dual cyclodextrin (CD) system composed of sulfated β‐CD and carboxymethyl‐α‐CD was selected as the chiral selector. A fractional factorial resolution V+ design was used for the identification of the critical process parameters, while a face‐centered central composite design and Monte Carlo simulations were employed for final optimization and defining the design space of the method. The experimental conditions of the working point were: 30 mM sodium phosphate buffer, pH 3.0, containing 40 mg/mL sulfated β‐CD and 7 mg/mL carboxymethyl‐α‐CD, capillary temperature 18°C, applied voltage ‐23 kV. Following the assessment of robustness by applying a Plackett‐Burman design, the method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guideline Q2(R1). The method allowed the quantification of the chiral impurity and three other related impurities at the 0.1 % level with acceptable accuracy and precision.

Comprehensive Review on Chiral Stationary Phases in Single-Column Simultaneous Chiral–Achiral HPLC Separation Methods

“…Different CD derivatives, such as native β-CD, phenylcarbamate-β-CD, and chlor-, or methyl-substituted phenylcarbamate-β-CDs are the most frequently applied forms of CSPs [ 74 ], prepared predominantly by different immobilization techniques, such as by ether or urea linkages [ 75 , 76 , 77 ], click-chemistry [ 78 ], etc. Besides their high versatility as chiral selectors, CDs already proved their chemoselective potential in electromigration techniques [ 79 , 80 , 81 , 82 ], as well as CSPs in the analysis of achiral compounds [ 83 , 84 , 85 ]. Until now, native β-CD [ 20 , 30 ] as well as its dimethylated [ 31 ] and phenylcarbamated [ 25 , 26 , 36 ] derivative CSPs have been applied in simultaneous chiral–achiral separations, including the bioanalytical determination of drug enantiomers and their metabolites, as well as methods developed for the quality control of pharmaceuticals.…”