Development of ledipasvir and sofosbuvir pure certified reference materials for improving quality of pharmaceutical analysis

The pure materials play a pivotal role in controlling the quality of pharmaceutical products, ensuring comparability and metrological traceability of test results, and performance evaluation of measuring instruments. Herein, the purity characterization of chronic hepatitis C virus sofosbuvir and ledipasvir pharmaceuticals was established based on the assessment of mass fractions of potential impurities in the material including heavy metals, residual solvents, and water content, as well as structurally related organic impurities. The combined estimate of these impurities by mass balance approach led to indirect purity determination of sofosbuvir and ledipasvir materials. The impurities mass fractions in each material were assigned by validated chromatographic methods, Karl Fisher titrator, and inductively coupled plasma-based method. The certified purity values of sofosbuvir and ledipasvir and their corresponding expanded uncertainties (k =2.0 at 95% CL) were found (99.79 +/- 0.03) %, (99.69 +/- 0.04) %, respectively. The developed certified reference materials (CRMs) with small uncertainty values will support pharmaceutical testing laboratories in their efforts to maintain and improve the quality of results and provide them with high-order CRMs for the accurate determination of both analytes in raw materials and finished products.