Chemical specifications for USP Purified Water are outlined in the Official Monograph by referencing Physical Tests chapters for conductivity and total organic carbon (TOC). Physical Tests Section <643> provides the TOC specification, capability of the TOC analyser, system suitability requirements, and calibration requirements. The section does not set forth requirements for online measurement versus grab sampling and laboratory analysis. Further, the section does not state the frequency of analysis. The TOC limit for USP Purified Water is 0.50 mg/L. The specification agrees with the current EP specification.
USP Physical Tests Section <645> outlines the specification for conductivity, method of determination, instrument, calibration requirements, etc. This section outlines a three-stage test method that compensates for the presence of carbon dioxide and pH. The most restrictive specification, Stage 1, is 1.3 µS/cm at 250C or 1.1 µS/cm at 200C, in agreement with the EP specification. The section does not set forth requirements for online measurement versus grab sampling and laboratory analysis. Further, the section does not state the frequency of analysis.
Other pharmacopeias may have additional testing requirements. As an example, the EP contains a nitrate specification of 0.2 mg/L, maximum. It is important to review the various pharmacopeial requirements for countries where products will be sold.
As indicated previously, certain systems may require supplemental sampling and monitoring for important contaminants not addressed specifically within the pharmacopeia. As an example, for a Purified Water system using ozone for microbial control (storage and distribution system), control of residual disinfecting by-products such as tri-halo-methanes may be critical. Ozone will oxidize tri-halo-methane compounds to carbon dioxide, which will react with water yielding the hydronium and bicarbonate ion, increasing the conductivity of Purified Water.