Method transfer assessment for boric acid assays according to different pharmacopoeias' monographs

Abstract

The background of this study was transfer assessment for H3BO3 assays according to different pharmacopoeias’ monographs and verification of the crucial parameters—the polyols’ excess (mannitol, glycerine, sorbitol), the initial H3BO3 concentrations and the indicator’s concentrations. The purpose of the work was the comparative study according to different pharmacopoeias: the European (EP 9), the American (USP 35-NF 30), the Japanese (JP XVII), important for quality control of H3BO3, as an active component or an excipient. pH analyses were set up to establish the effects of selected polyols and the initial H3BO3 concentrations. For evaluation of assay results and methods’ equivalence, standard t test and two one-sided t test (TOST) were applied. Pharmacopoeias’ procedures propose volumetric analyses by 1 M NaOH standard solution with visual end-point detection (phenolphthalein) using sufficiently high H3BO3 concentrations and less excess of polyols, as the good alternative to potentiometric method. The influence of phenolphthalein’s concentration (0.1%, 1%), evidenced as relevant factor, caused the difference shown by standard t test: 99.82% (EP 9) and 99.66% (JP XVII). Equivalences between three methods were confirmed by TOST procedures with defined acceptance criterion ± 2% derived from the mean value (99.83%). The comparative study results pointed out that the initial phenolphthalein’s concentration was the crucial influencing factor on harmonization of assay mean values, which was confirmed by TOST application for the methods’ equivalency in method transfer evaluation. The best possible correlation between the lowest excess of polyol-sorbitol and the highest initial boric acid concentration was proved by JP XVII, which was indicated by pH-metric analyses. Graphic abstract: [Figure not available: see fulltext.]