Development and validation of an UPLC method for the rapid separation of positional isomers and potential impurities of rivastigmine hydrogen tartrate in drug substance and drug product

摘要

Although a number of methods are available for evaluating Rivastigmine hydrogen tartrate (RIV) and its possible impurities, a common method for separation if its potential impurities and positional isomers with good efficiency remains unavailable. With the objective of developing an advanced method for rapid separations with shorter runtimes, a simple, precise, accurate stability-indicating gradient reverse phase ultra-performance liquid chromatographic (RP-UPLC) coupled with a photodiode array detector method was developed for the quantitative determination of RIV and its impurities in drug substance and drug product. The determination was done for an active pharmaceutical ingredient, its pharmaceutical dosage form in the presence of degradation products, and its process-related impurities. Chromatographic separation was achieved on Acquity UPLC BEH Phenyl (100mm x 2.1 mm, 1.7 μm) column with a mobile phase containing a gradient mixture of solvents A and B. The compounds eluted within a short runtime of 10 min and were monitored at 210 nm with the flow rate and the column oven temperature of 0.4 mL/min and 40°C, respectively. The resolution of RIV and its eleven impurities (positional and potential) was greater than 2.0 for all pairs of components. The newly developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness. Forced degradation studies were also performed to demonstrate the stability indicating power of the developed UPLC method.