GE
Water & Process Technologies
Analy tical Instruments
Application Note
Using the Sievers* 800 TOC Analyzer in Cleaning
Validation Applications
An increasing number of pharmaceutical and biopharma-ceutical companies are realizing the benef its of using total organic carbon (TOC) over more traditional methods for cleaning validation applications. As companies begin their method development process, some applications-related questions have arisen. The questions range from how to get started w ith method development to how to optimize analysis conditions. This technical note offers a few sugges-tions to help you optimize the performance of your Sievers* 800 TOC Analyzer for cleaning validation applications.
Verify Solubility of the Solution When pH 2
The Sievers 800 is designed to measure the TOC of aque-ous solutions and as part of the measurement process an adjustment of the sample pH is made to achieve a pH of approximately 2. Altering the pH of an aqueous solu-tion can affect the solubility of the target compounds.
For example, acidif ication of a basic or neutral solution may cause precipitates to form. At the time of acidif ica-tion within the analy zer, precipitaica-tion can occur resulting in a clogging of the instrument’s flow path. Therefore, it is important to verify that the target compounds are sol-uble in acidic conditions. To verify the solubility , place a small aliquot (1-2 mL) of the solution to be analy zed into a test tube or vial. Then acidify the sample with 6 M phosphoric acid until it is pH 2 (2-3 drops). Visually inspect the acidif ied aliquot for evidence of precipitate formation. This will simulate the environment within the analy zer and ensure compatibility .
If no precipitate has formed, then the solution may be analy zed directly . If a precipitate has formed, then pre-pare dilutions of the test solution. Acidify and observe these dilutions using the technique described above. When the precipitation no longer occurs upon acidif ica-tion, the solution may be analy zed using TOC testing.
Ensure that the Instrument 's Effluent is pH 2
Use a strip of pH paper to verify that the effluent (waste stream) of the analy zer has a pH of 2. When analy zing buffered solutions, the acid flow rate may need to be adjusted to ensure this low pH.
Analysis of Basic Solutions
Some cleaning applications may require basic conditions. When using concentrations greater than 0.03 M NaOH or KOH, a neutralization (or acidif ication) step prior to analy-sis is necessary. Also, basic solutions have the tendency to absorb high concentrations of CO2, and therefore, the ratio
of IC:TOC may exceed 10:1. This issue is discussed in fur-ther detail in the Sievers 800 User's Manual.
Refer to Case Study
For general ideas concerning how to get started with method development for y our cleaning validation appli-cation, refer to the application note, TOC Analysis of Compounds w ith Low Water Solubility ; Evaluation of Sw ab Recoveries for Cleaning Validation Applications.For further questions regarding y our particular application, please contact us for application support .
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