Development and validation of a photometric titration method: Spotlighting!

Introduction
Photometric titration combines classical titrimetry with photometric detection to quantify the concentration of analyte in solution. In contrast to manual titration using a burette, this analytical technique has the advantage of being automated and objective, i.e. not operator-dependent, while ensuring traceability of the assay.
The aim of this project is to develop and validate a photometric titration method.

Materials and method
Citric acid (C₆H₈O₇) has been used like test, its assay involving the following acid-base reaction: 3NaOH + C₆H₈O₇ → 3H₂O + Na₃C₆H₅O₇. Photometric titration was performed using an automatic titrimeter (Mettler Toledo T5) equipped with the DP5 phototrode and a sodium hydroxide solution (NaOH) standardised to 0.1 mol/L. The equivalence point was detected at 590 nm by the phototrode thanks to colour change of the indicator (phenolphthalein). The method was validated in accordance with the recommendations of the US Pharmacopoeia (USP), the International Council for Harmonisation (ICH) Q2 R(1) guideline and the manufacturer’s reference (Mettler Toledo).
Validity criteria included 5 calibration points with a coefficient of determination R² > 0.995 and accuracy (precision and trueness) evaluated over 3 days with coefficients of variation (CV) < 3%. Reproducibility over 3 days and the limit of quantification (LOQ) were also analysed.

Results
The titration method was linear (R² = 0.997). Concerning the intra- and inter-day accuracies, all CV were below than 1%. The relative differences compared with the theoretical values ranged from 0.34% to 1.91%, and the trueness was therefore judged to be satisfactory. The LOQ has been determined at 0.02 g/L.

Conclusion - Discussion
The requirements for validation of photometric titration method have been met. This method can therefore be applied routinely to control of the citric acid solution produced by our preparatory unit. This titration technique has the advantage of being robust, easy and fast. It is particularly well adapted to pharmaceutical controls thanks to its precision and traceability system. This validation protocol will be used to validate futures analytical methods using titrimetry.

See the poster