Validation of an Assay Method for an Aqueous Solution of Trichloroacetic Acid: Benefits of Automated Acid-Base Titration

Introduction
The aqueous solution of trichloroacetic acid (TCA) dosed at 33% (w/w) is indicated for xanthomas and inflammatory granulomas of the inner ear. The solution is a hospital preparation (HP), prepared as cutaneous or transmucosal application and thus is subjected to final content control according to requirements of the European Pharmacopoeia (Ph. Eur.). The main objective of the study is to validate the titrimetric (acid-base) assay method for the TCA solution.

Materials and methods
The assay was performed using an automatic titrator (Mettler Toledo T5 equipped with a DGi-115-SC glass electrode) and a titrating solution of sodium hydroxide, NaOH at 0.1 mol/L. The validation method was done according to the United States Pharmacopoeia (USP) Recommendations for titration methods validation, the International Council for Harmonization (ICH) guideline Q2 R(1), and the reference: Validation of titration, a guideline for regulated laboratories by Mettler Toledo. The accuracy and precision of each measurement were determined by the relative difference (RD) between the measured concentrations and the theoretical concentrations, in the addition, the relative standard deviation (RSD) between the measured concentrations was calculated. According to the recommendations, the RD and RSD have to be below 3% to meet the recommendations. Linearity was tested with a 5-point range covering 80 to 120% of the final target concentration. The test is validated if the determination of the coefficient R2 is greater than 0.995. Reproducibility was evaluated by performing titrations on three different days. The determination of the limit of quantification (LOQ) was also carried out.

Results
The accuracy and precision tests are validated. The average relative difference is 1.63% (all values between 1.12 and 2.16%). The average relative standard deviation is 0.24% (all values between 0.05 and 0.49%). The method is linear (R2 = 1) and reproducible (all coefficients of variation are below 3%). The LOQ is 0.83% (w/w).

Discussion-conclusion
The automated acid-base titrimetric assay method is validated. This method is precise, accurate, and reproducible. Therefore, this assay can be routinely used for the final control of the 33% TCA HP. It will help to optimize the control time of the operator and ensure traceability of the assays performed.

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