Using the Sievers 800 TOC Analyzer in Cleaning Validation Applications
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 biopharmaceutical 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 suggestions 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 aqueous 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 solution 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 ication within the analy zer, precipitation can occur resulting
in a clogging of the instrument’s flow path. Therefore, it
is important to verify that the target compounds are soluble 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 prepare dilutions of the test solution. Acidify and observe
these dilutions using the technique described above.
When the precipitation no longer occurs upon acidif ication, 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 analysis 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 further 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 application, 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 .
* Trademark of General Electric Company; may be registered in one or more countries.
For more information, visit w w w.GEinstruments.com. Find a sales partner near you through the “Contact Us” Section.
USA
GE Analy tical Instruments
6060 Spine Road
Boulder, CO 80301-3687 USA
T +1 800 255 6964
T +1 303 444 2009
F +1 303 444 9543
[email protected]
www.geinstruments.com
Europe
Unit 3 Mercury Way
Mercury Park Estate
Trafford Park
Manchester, UK M41 7LY
T +44 (0) 161 866 9337
F +44 (0) 161 866 9630
© 2005, General Electric Company . All rights reserved.
300 00008 Rev A
MC05-085
Water & Process Technologies
Analy tical Instruments
Application Note
Using the Sievers* 800 TOC Analyzer in Cleaning
Validation Applications
An increasing number of pharmaceutical and biopharmaceutical 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 suggestions 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 aqueous 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 solution 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 ication within the analy zer, precipitation can occur resulting
in a clogging of the instrument’s flow path. Therefore, it
is important to verify that the target compounds are soluble 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 prepare dilutions of the test solution. Acidify and observe
these dilutions using the technique described above.
When the precipitation no longer occurs upon acidif ication, 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 analysis 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 further 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 application, 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 .
* Trademark of General Electric Company; may be registered in one or more countries.
For more information, visit w w w.GEinstruments.com. Find a sales partner near you through the “Contact Us” Section.
USA
GE Analy tical Instruments
6060 Spine Road
Boulder, CO 80301-3687 USA
T +1 800 255 6964
T +1 303 444 2009
F +1 303 444 9543
[email protected]
www.geinstruments.com
Europe
Unit 3 Mercury Way
Mercury Park Estate
Trafford Park
Manchester, UK M41 7LY
T +44 (0) 161 866 9337
F +44 (0) 161 866 9630
© 2005, General Electric Company . All rights reserved.
300 00008 Rev A
MC05-085