Unique liquid chromatography technique for the determination of mirabegron in the presence of polymers; robustness by Design Expert in the light of Quality by Design.

Abstract

The current study is designed to estimate mirabegron in the presence of high molecular weight polymers using a unique liquid chromatography method and sample preparation technique. The proposed method is significant because of the many analytical issues faced during the development studies. Based on the experimental results, we finally achieved the stability-indicating power of the method. The adequately prepared mobile phase was in the ratio of pH2.0 buffer and acetonitrile (80:20) v/v, and the buffer pH2.0 was prepared as follows: 8.7ml of perchloric acid, 2ml of triethylamine and 3.0g sodium hydroxide into 1L of water mixed well. The system suitability parameters were achieved using a Waters X-Bridge C18 (4.6 × 150 mm, 3.5μm) column and mobile phase. The optimized chromatographic conditions included a column temperature of 45°C, a flow rate of 1.0ml min-1 ; an injection volume of 5μl, UV 247 nm, and 15 min runtime. The method was validated and transferred to quality control as per International Conference on Harmonization Q2(R1) and the Chinese Pharmacopoeia 2020 edition <9101> and <9100>. The recovery and linearity results were obtained between 99.0 and 101.0%; the value of r2 was 0.9998. The method robustness study was established by utilizing the Design of Experiments part of the Quality by Design concept. The method's stability-indicating nature was proved by a forced degradation study; all of the conditions for analyte peak purity were passed, and mass balance was achieved. The method was used to determine mirabegron assay, as well as content uniformity, blend uniformity and cleaning samples. It is a user-friendly and cost-effective method.