Total organ
IC carbon (TOC) is an indirect measure of organ
IC molecules present in pharmaceut
ICal waters measured as carbon. Organ
IC molecules are introduced into the water from the source water, from purif
ICation and distribution system materials, and from biofilm growing in the system. TOC can also be used as a process control attribute to monitor the performance of unit operations comprising the purif
ICation and distribution system.
A number of acceptable methods exist for analyzing TOC. This chapter does not limit or prevent alternative technologies from being used, but provides guidance on how to qualify these analyt
ICal technologies for use as well as guidance on how to interpret instrument results for use as a limit test. The Standard Solution is a theoret
ICally easy-to-oxidize solution that gives an instrument response at the attribute limit. The analyt
ICal technology is qualified by challenging the capability of the instrument using a theoret
ICally diff
ICult to oxidize solution in the system suitability portion of the method.
Analyt
ICal technologies utilized to measure TOC share the objective of completely oxidizing the organ
IC molecules in an aliquot of sample water to carbon dioxide (CO2), measuring the resultant CO2 levels, and expressing this response as carbon concentration. All technologies must discriminate between the inorgan
IC carbon, wh
ICh may be present in the water from sources such as dissolved CO2 and b
ICarbonate, and the CO2 generated from the oxidation of organ
IC molecules in the sample.
Two general approaches are used to measure TOC. One approach determines TOC by subtracting the measured inorgan
IC carbon (
IC) from the measured total carbon (TC), wh
ICh is the sum of organ
IC carbon and inorgan
IC carbon:
TOC = TC –
IC.
The other approach first purges the
IC from the sample before any carbon measurement is performed. However, this
IC purging step also purges some of the organ
IC molecules, wh
ICh can be retrapped, oxidized to CO2, and quantitated as purgeable organ
IC carbon (POC). The remaining organ
IC matter in the sample is also oxidized to CO2 and quantitated as nonpurgeable organ
IC carbon (NPOC). In this approach, TOC is the sum of POC and NPOC:
TOC = POC + NPOC.
In pharmaceut
ICal waters, the amount of POC is negligible and can be discounted. Therefore, for the purpose of this methodology, NPOC is equivalent to TOC.