Background and Importance Ampoules with sodium perchlorate 100 mg/ml for injection are manufactured at the Hospital Pharmacy for use as a premedication before certain nuclear imaging procedures. The Quality Control department recently became aware that pH measurements during quality control were varying more than expected between batches, resulting in out of trend/specification results as well as greater variation between in-process and release values. No data explaining these variations could be found in the literature.

Aim and Objectives To determine factors which could cause unstable pH measurements of sodium perchlorate solutions, and if changing the pH electrode could solve the problem.

Material and Methods pH-meter: Mettler Toledo SevenExcellence S400-Bio, pH-electrodes: (A) InLab Routine Pro-ISM (Reference electrolyte: potassium chloride (KCl) 3M); (B) InLab Science Pro-ISM (Reference electrolyte: KCl 3M); (C) InLab Expert Pro-ISM (Reference electrolyte: XEROLYT®-polymer).

To establish the influence of external factors, pH was measured over time in different types of vials (glass/plastic) and with extended exposure of solution to air. Comparison of electrodes: pH was measured uninterrupted at regular intervals for 420 seconds (n=3). Raman spectra of the precipitates were acquired by using a WITec Alpha300 Apyron Confocal Raman Microscope.

Results Different types of vials as well as extended air exposure of solution did not result in significant change of pH values. Initial testing with electrode A resulted in a characteristic trend where the pH increased, stabilised, and then decreased, while electrode C remained stable. For electrode B the same trend was observed as for electrode A, but testing was aborted due to visible precipitation in the sample. The precipitates were identified as Potassium perchlorate by Raman spectroscopy. Results from subsequent comparison is shown in table 1 (mean±SD).

Conclusion and Relevance The unreliable results could be attributed to an interaction between sodium perchlorate and KCl reference electrolyte. This also created a precipitation, more clearly visible in electrode B due to higher flow of reference electrolyte to the sample than electrode A. Electrode C with polymer electrolyte was the most stable, without the characteristic decrease in pH after the initial stabilisation, and no precipitation.

Conflict of Interest No conflict of interest.