VALIDATION OF THE SPECTROPHOTOMETRIC PROCEDURE FOR DESLORATADINE ASSAY IN TABLETS APPLYING THE UNCERTAINTY CONCEPT OF THE STATE PHARMACOPOEIA OF UKRAINE

Aim. This work aimed to validate an assay procedure for desloratadine tablets by direct spectrophotometric method. Materials and methods. A pilot-scale batch of the pharmaceutical preparationAlerdez, film-coated tablets containing 5 mg of desloratadine, manufactured by PJSC SIC “Borshchahivskiy CPP”, Ukraine, was used as an object of the study. A UV-Vis spectrophotometer Lambda 25 (Perkin Elmer), analytical balance Mettler Toledo XP 205DR, and class A volumetric apparatus were used in the study. Validation of the procedure was performed following the metrological approach of the State Pharmacopoeia of Ukraine (SPhU), whose requirements for the target uncertainty and bias, which rest on the risk assessment of making incorrect decisions on compliance (a confidence level of 95 %), were translated into criteria for all validation characteristics recommended by ICH. All calculations were made in normalised coordinates. The linearity, accuracy and precision (repeatability) were studied in a single experiment using nine different concentrations that uniformly covered the range of ±30 % from the nominal concentration of desloratadine. For validation of the procedure, an SPhU reference standard of desloratadine was used. Results. The experiment design and validation characteristics being tested were in full compliance with ICH Q2(R1) recommendations. All performance characteristics conformed to the criteria recommended by the SPhU. Requirements for the target uncertainty (1.6 %) and bias for any systematic source of variation (≤0.51 %, negligible in relation to 1.6 %) were established. The analytical procedure was specific – the absorbance from the placebo solution was insignificant (A %=0.36). The procedure met the requirements for linearity, accuracy, and precision at the repeatability level. The residual standard deviations0was 0.34 (≤ 0.84); correlation indexRcwas 0.9998 (≥0.9991); interceptаwas 0.045 (less than its confidence interval ∆a=1.14). The confidence interval for recovery∆Z, which was used as a precision estimate, was 0.55 % (less than the target uncertainty). The mean recovery, which was used as an accuracy estimate, statistically insignificantly deviated from 100% (|Zmean‑100| = 0.022 %). The confidence interval for the intermediate precision∆intrawas 0.33 % (less than the target uncertainty). The developed analytical procedure was found to be robust. Conclusions. A spectrophotometric procedure suitable for the assay of desloratadine in film-coated tabletsAlerdezwith content limits of ±5 % was validated by the SPhU approach.