Development of a rapid and validated stability-indicating UPLC-PDA method for concurrent quantification of impurity profiling and an assay of ipratropium bromide and salbutamol sulfate in inhalation dosage form

Abstract

The objective of the proposed work was to develop a rapid and new reverse phase ultra-performance liquid chromatographic (RP-UPLC) method for the simultaneous quantification of related impurities of ipratropium bromide and salbutamol sulfate in the combined inhalation dosage form. Herein, the chromatographic separation was achieved on Acquity BEH C18 (100mm×2.1mm, 1.7μm) column by following gradient elution of solvent A as 2mM potassium dihydrogen phosphate with 0.025% of 1-pentane sulphonic acid sodium salt (pH 3.0 buffer) and solvent B as pH 3.0 buffer, acetonitrile and methanol in the ratio of (32:50:18, v/v/v) at a flow rate of 0.3mL/min. The samples were detected and quantified at 220nm. To prove the stability-indicating potential of the method, forced degradation studies were performed using acidic, basic, oxidative, thermal, and photolytic conditions. After sufficient exposure, the resultant solutions were injected and found that all degradants and impurities formed during stress studies were well separated from each other and from the main peak compounds. The performance of the method was validated according to the present ICH Q2 (R1) guidelines. The method has good linearity (r≥0.999) and consistent recoveries were obtained with a range of 91.3-108.8% for all compounds. The % RSD obtained for the precision experiments was less than 5% and also there is a good sensitivity (LOQ≤0.5μg/mL) for all compounds. The intended method proved its applicability and that it can be beneficial to pharmaceutical industries for quick quantification of related impurities and assay in quality control department for analysis of ipratropium bromide and salbutamol sulfate inhalation dosage form.