TOC determination
TOC stands for Total Organic Carbon and is a sum parameter in water analysis. It therefore provides information on the contamination of purified water or ultrapure water by carbon-containing organic compounds. The TOC value represents the sum of the total carbon with a very low limit of detection (“LOD”) in the sample. The analysis method used at BioChem is based on catalytic combustion on the catalytic combustion of the sample. An aliquot of the sample is burned in a furnace at up to 950 °C using a catalyst. The carbon contained in the sample is oxidized to carbon dioxide (CO2) and is then analyzed and evaluated using an infrared detector (NDIR detector).
In water analysis, the TOC value of ultrapure water is an important sum parameter to ensure process and product safety in the pharmaceutical and active ingredients industry. In addition, regular monitoring of the water using TOC measurement allows problems and faults to be detected quickly and at an early stage. This leads to less production plant downtime.
TOC is an established and monographed analysis method in the pharmaceutical industry and in the environmental sector (Ph. Eur. 2.2.44 / USP <643>) to test the purity of water fast and easily. The TOC determination can also be used for cleaning validation in order to check for residues of active ingredients, solvents and cleaning agents.
Determination of the nitrogen content
BioChem's portfolio includes two analytical methods for determining the nitrogen content: TNb analysis and Kjeldahl nitrogen determination.
The TNb value (total bound nitrogen) is also a sum parameter. It includes nitrate, nitrite, ammonium and organic nitrogen-containing compounds, such as amino acids. The analysis method at BioChem is based on a combustion process and detection using chemical luminescence. The nitrogen monoxide (NO) produced during combustion is converted to nitrogen dioxide (NO2) in an excited state using ozone. When it returns to its ground state, light quanta are generated which are detected. The generated radiation intensity is proportional to the generated NO concentration of the combustion, which in turn correlates with the nitrogen content of the sample solution.
TNb analysis is mainly used for the determination of impurities in various water samples (e.g. eutrophication of water bodies). However, this method has been gaining importance in the pharmaceutical industry for several years, particularly in the field of biologics for cleaning validation. Compared to the individual determination of nitrogen compounds, TNb analysis is faster and less time-consuming. Especially in combination with TOC analysis, a statement can be made fast and reliably about any residues in rinse samples after cleaning. This is particularly important as the cleaning agents used for biologicals do not usually contain nitrogen and can therefore be distinguished from product residues.
As an alternative to TNb analysis, Kjeldahl nitrogen determination is used in the pharmaceutical and chemical industries, as well as in food and environmental analysis, especially for inhomogeneous or solid samples. The Kjeldahl method is a classic, monographed analytical method (Ph. Eur. 2.5.9 / USP <461>). In this method, a sample weight is digested with sulphuric acid using a catalyst. This converts the nitrogen compounds contained into ammonium sulphate. The amount of ammonium sulphate produced is finally converted into ammonia in further process steps and this is quantitatively determined by titration.
Cleaning validation
In recent years, the importance of the cleaning process for product and process safety has increased significantly. Cleaning is no longer seen as a necessary evil, but as an important process step that must also be optimized and validated. The success of a cleaning process can only be assessed using suitable sampling and analysis methods. There are two main types of sampling. There is sampling using the swab test and the rinse. In the swab method, critical points on the surface of a system in contact with the product are sampled by wiping with swab sticks (direct sampling). The rinse method, on the other hand, is an indirect method in which the process system is rinsed and a rinse sample is filled. The type of sampling has a direct influence on the analysis and should be validated by means of recovery studies. Staff training and standardized execution are also of great importance. The swab or rinse samples can be analyzed for sum parameters using TOC/TNb analysis. Specific analysis methods using LC or GC to determine individual components are also possible. In project-specific cases, a correlation of the TOC content with active ingredient residues can also be useful.
What does BioChem Labor für biologische und chemische Analytik GmbH offer you?
BioChem offers its customers routine and rapid water analysis (TOC) of WFI and ultrapure water. On request, analyses of the TNb value (total bound nitrogen) can also be carried out. Alternatively, BioChem offers nitrogen determination according to Kjeldahl for raw materials or pharmaceutical samples.
In addition, BioChem's experts are available with their analytical know-how for cleaning validation and can also identify and quantify solvents or residual active ingredients using GC and LC.
By the way: BioChem also carries out microbiological tests including sterility and testing for bacterial endotoxins on water. This enables us to provide you with comprehensive support in the qualification of water systems.
Please contact us if you are interested, our analytical experts will be happy to provide you with further information.
