Wednesday 31 March 2010

Help on: TOC vs HPLC for Cleaning Validation


Do you have any problems relating to analytical chemistry for pharmaceuticals or training? Send your questions to the MTS helpdesk using our contact form.

"I want to know whether TOC analysis is better than HPLC for cleaning validation?"

"The use of Total Organic Carbon (TOC) as an analytical test for cleaning validation has increased rapidly in recent years. This is due to a number of factors including:

  • It is very easy to use;
  • The actual testing can be carried out very quickly;
  • TOC testing requires very little method development and is easy to validate;
  • One method can be used for all cleaning samples; and
  • It is a cost effective analytical technique.

TOC measures all the carbon in the sample and is thus a non-specific technique; this can be viewed as both an advantage and disadvantage. On one hand it means that all carbon which can be oxidised under TOC conditions can be detected and thus the result provides a measure of all contaminants. On the other hand it does not determine the amount due to the active substance. The result may be considered as ‘worst case’, assuming that the entire residue is due to the active substance.

To use TOC for cleaning analysis, you need to establish that the contaminating material is organic and contains carbon that can be oxidised under the TOC test conditions; some organic compounds cannot be reliably detected using TOC. Use of TOC requires that the contaminant is at least slightly soluble in water.

As to which is better, TOC or HPLC, it will depend on the contaminating substances you are testing for. The advantages of TOC make it preferable but there are times when it will not be suitable, in which case HPLC may provide a better option. The effort involved in validation of cleaning means that it is not usually beneficial to switch established processes from HPLC to TOC. However for new processes TOC may provide a good solution.”