TOC Performance Test as per Japanese Pharmacopoeia Application Note · multi N/C pharma

Meeting TOC Analyzer Requirements for Pharmaceutical Applications in Japan Introduction

A System Suitability Test (SST) or Performance Test has to be performed at regular intervals to check the suitability of a TOC analyzer for the use in pharmaceutical applications. This test solely serves to check the digestion capacity of the analyzer, i.e., the CO2 yield in complete oxidation of the analytes. By definition, the SST must be performed using two standard substances: one readily oxidizing compound is used as the reference, while the other poorly oxidizing compound is used as the test substance. The calibration of the device should be performed with the reference substance.

In contrary to the European and U.S. pharmaceutical regulations (Pharm. Eur., USP) which prescribe sucrose and p-benzoquinone as reference and test substances, the Japanese Pharmacopoeia 17, General Tests section 2.59, prescribes potassium hydrogen phthalate as reference substance (standard solution) and sodium dodecyl benzene sulfonate as test substance (test solution).

The analyzer should be capable of generating not less than 0.450 mg/L of total organic carbon when measuring a solution containing 0.806 mg/L of sodium dodecyl benzene sulfonate (nominal TOC concentration of 0.500 mg/L) as sample. In case, the required recovery rate of minimum 90 % is not achieved it may be necessary to replace the catalyst (high-temperature combustion systems) or check the oxidation reagent or exchange the UV lamp (UV/wet chemical digestion systems).

According to the Japanese TOC monograph a TOC analyzer applied for pharmaceutical water testing must provide a sufficient sensitivity to measure the amount of TOC down to 0.050 mg/L. It is also stated that the reagent purity of water used to prepare standard solutions or reagents (for oxidation or TIC decomposition) should not contain more than 0.250 mg/L TOC. This application note clearly demonstrates that the instruments of the multi N/C pharma series meet all performance requirements according to Japanese Pharmacopoeia.