Innovation in UV Oxidation Direct Conductivity TOC Measurement to Improve Accuracy and Precision
7Pages

Reprinted from PHARMACEUTICAL ENGINEERING quality systems THE OFFICIAL TECHNICAL MAGAZINE OF ISPE Innovations in UV Oxidation Direct Conductivity TOC Measurement to Improve Accuracy and Precision by Roger Schmid and Randy Turner This article presents innovations to improve the accuracy and reliability of UV oxidation direct conductivity TOC measurement methods. otal Organic Carbon or TOC is the carbon whose origin is organic in nature. It can originate from naturally occurring organic acids, such as tannic acid, bacteria, and abrasion of valves. The measurement of TOC is critical to the pharmaceutical industry because various regulatory bodies have established limits for TOC in Water for Injection (WFI) and other uses of water in pharmaceuticals. The main regulatory guidelines are incorporated in the following: 1. USP<643>, “Total Organic Carbon,” United States Pharmacopoeia 36-NF 31, U.S. Pharmacopeial Convention Inc., Rockville, Md. (2013). 2. USP<645>, “Water Conductivity,” United States Pharmacopoeia 36-NF 31, U.S. Pharmacopeial Convention Inc., Rockville, Md. (2013). 3. USP<1231>, “Water for Pharmaceutical Purposes,” United States Pharmacopoeia 36-NF 31, U.S. Pharmacopeial Convention Inc., Rockville, Md. (2013). 4. EP 2.2.38, “Conductivity,” European Pharmacopoeia, vol. 7.0, Council of Europe, Strasbourg, France (2013). 5. EP 2.2.44, “Total Organic Carbon in Water for Pharmaceutical Use,” European Pharmacopoeia, vol. 7.0, Council of Europe, Strasbourg, France (2013). 6. JP 4.5.2, “Monitoring of TOC as the Indicator for Organic Impurities,” JP XVI. To measure TOC, the organic molecules must be reduced to inorganic carbon allowing quantitative measurement of the resultant carbon dioxide CO2. The organic molecule can be decomposed to inorganic carbon by thermal decomposition, UltraViolet (UV)-persulfate oxidation, and direct UV oxidation. The following are common methods of TOC analysis: 1. 2. 3. 4. Thermal decomposition with NDIR detection UV-persulfate oxidation with NDIR detection UV-persulfate oxidation with conductivity detection Direct UV oxidation with conductivity detection Each process is based on the oxidation of the organic carbon that is present in the water and the subsequent measurement of the carbon dioxide which results from the oxidation. These methods all have advantages and disadvantages depending on how the oxidation and measurements are technically carried out. Therefore, each application has to be irst examined as to which of the different methods is the most suitable. Methods of TOC Analysis Thermal Decomposition With this process, the organic particles are destroyed by high temperatures. In this way, the undissolved components (suspended solids or wear debris) are also completely decomposed - Figure 1. This is a common method particularly with a high TOC load (e.g., municipal sewage). UV-Persulfate Oxidation with NDIR or Conductivity Detection The wet-chemical oxidation with UV light and persulfate is, PHARMACEUTICAL ENGINEERIN

quality systems TOC Measurement Methods Figure 1. Schematic diagram of thermal decomposition. Figure 2. Schematic diagram of UV-persulfate decomposition. especially with puriied water and ultrapure water applications, widely spread and accepted as “the standard.” A great advantage of this method is the large operational range of less than 1 part per billion (ppb) to more than 100 parts per million (ppm) with high accuracy. • TC Total Carbon The sum of inorganic and organic carbon (TIC plus TOC), the value of which is determined by the second sensor • TOC Total Organic Carbon The component...

quality systems TOC Measurement Methods 1. Stabilization of the thermal conditions 2. Increase of radiation lux 3. Optimization of the sample low A few measures and modiications had to be developed to reach this goal. All the presented changes had a huge effect on the method presented below. Stabilization of the Thermal Conditions The direct UVmethod is strongly Figure 4. Reactor with a heat exchanger. inluenced by temperature effects. Due to the energy transfer from the UVlamp, the sample temperature will be increased up to 10°C from conductivity sensor 1 to 2. The conductivity has to be...

quality systems TOC Measurement Methods realized in combination with an optimized sample low. The classic design of a UV lamp and the sample is lowed around the light source. Divergence loss and relection are practically unavoidable. The formation of deposits on the directly radiated surface, which decreases radiation density, cannot be fully eliminated in long running operations. This side effect can only be avoided by establishing a direct contact between the UV lamp and the sample. Figure 7 demonstrates the sample low in the newly engineered UV reactor. The sample lows directly along the...

TOC Measurement Methods The calibration in linear mode occurs through the measurement of an exactly defined sample solution (Sucrose 1 ppm). Based on the measurement result, the instrument calculates the effective slope, which it displays. From experience, the values are in the range of 0.15 to 0.3. Pharmaceutical Application Measurement Points In modern WFI and Pure Water (PW) plants, most measurements are made at the points mentioned below: Typically in pharmaceutical plants, it is after the distillation, in the storage tank, at the entrance and exit of the loops and of course at the...

quality systemsTOC Measurement Methods chemical distributor as long as they comply with the quality requirements for an analysis. Simple Grab Sample Testing An extra benefit of the operating process is the possibility of examining grab samples with the instrument. The sample is drawn through the instrument by a peristaltic pump, regardless of whether it is an SST sample, a functional test or a grab sample - Figure 9. Grab samples are easily connected and can be measured immediately by the press of a button. As long as the grab sample measurement mode is active, the signal outpoints of the...