A STUDY OF THE INFLUENCE OF THE TEST SAMPLE INHOMOGENEITY ON VARIABILITY IN ASSAY RESULTS OF DESLORATADINE IN FILM-COATED TABLETS

Aim. The work aimed at metrological evaluation and management of the risk of inconsistency in the results of desloratadine assay in film-coated tablets.

Materials and methods. A pilot-scale batch of the pharmaceutical preparation Alerdez served as a study object. Spectrophotometric readings were performed on a UV-Vis spectrophotometer Lambda 25 at 282 nm. An analytical balance Mettler Toledo, pH-meter Metrohm, Class A volumetric pipettes and flasks were used for analysis. The test sample was prepared by manual tablet grinding.

Results and discussion. A trend of obtaining inconsistent assay results with a systematic shift towards an increase while taking test portions in sequence was observed. This may inform a test sample inhomogeneity, which may be reduced by increasing a test portion mass. An experiment design to study the impact of the test portion mass on the variability in assay results was laid down. A prognosis for the minimum test portion mass contributing to the mitigation of the risk of the test sample inhomogeneity was scientifically justified and experimentally verified. Acceptance criteria for the assessment of the test sample homogeneity by assay results were established based on the principle of insignificance and recommendations of the State Pharmacopoeia of Ukraine to the target measurement uncertainty. A procedure for desloratadine assay intended to be used for the method transfer and routine analysis, as well as acceptance criteria for assay results, was developed. Their feasibility was experimentally proved during method transfer. The greater difference between the values obtained in the receiving unit compared to those collected in the sending unit was observed, yet the results met the acceptance criteria.

Conclusions. This paper provides comprehensive solutions that allow for minimizing the risk of variability in desloratadine assay results. The risk of aberrant assay results could be mitigated by using a test portion equivalent to the weight of four tablets (approx. 420 mg)