化学药中特殊物质和基团检测方案

智能文字提取功能测试中

analytikjena analytikjena Application field / industrybranch： Chemistry/ Polymer IndustryElectronics Energy Nutrition /Agriculture Geology /Mining Semiconductor Technology Clinical Chemistry /Medicine /Sanitation/Health Care Cosmetics Material Analysis Metallurgy/Electroplating Pharmacy Refineries /Petrochemistry Environment/Water/Waste Other TOC analysis in cleaning validation and product control within thepharmaceutical industry - Use of the multi N/C pharma UV Author： Bernd Bletzinger， Analytik Jena AG Introduction TOC analysis has become a routine parameter in the pharmaceutical industry used both formonitoring quality of the ultrapure water supply for laboratory and production and for the mappingof cleaning validation for production systems. In addition to TOC online or inline analysis， TOC labanalyzers are also frequently used. To minimize or prevent cross contamination in production facilities of the pharmaceutical industry，companies are obliged to purify the production equipment following a defined procedure inaccordance with the pharmaceutical operating regulations and the EC guidelines for good practicein the manufacture of medicaments. These definitions are usually issued via cleaning SOPs andsubordinated work instructions. The effectiveness of these cleaning procedures must additionallybe proven via analytical measuring methods called cleaning validation. This means that after successful cleaning a check must be carried out for residue of activeingredients， additives， detergents and their decomposition and reaction products， using arepresentative and validated sampling and analysis method. A cleaning validation normallycomprises such a check in three successive batches and a corresponding revalidation after adefined period of time. However， the difficulty in this analysis lies in the fact that the still tolerable contamination is usuallyof the magnitude of the verification and detection limits for the analysis methods used. Status of the TOC parameter Both analysis methods specific to active ingredients， such as HPLC， GC etc.， and non-specific so-called summation parameters， such as TOC-/ TN， analyzers and measuring instruments formeasuring conductivity， pH value and surface tension， are in use. In particular with complex products or product combinations as well as various detergents， theTOC analysis plays an important role in the cleaning validation. Since carbon is present in all organic compounds， TOC detection permits the detection andquantification of organic residues of active ingredients， additives， reaction products and detergentsin the trace element range around and below 50 ppb and is thus predestined to be a so-calledscreening parameter. According to PharmEur. 2.2.44cand USP <643> TOC detection is5ca pharmacopoeia method used already for the characterization of the organic contamination of waterand ultrapure water， and the validation effort is significantly reduced compared to other analysismethods. Sampling and analysis methods Two strategies are followed during cleaning validation to prove the purity of the productionsystems. In the post-final rinse the system is rinsed once more after the final rinse of the cleaningprocedure to transfer any existing organic residue into this rinse water and thereby make itavailable for TOC measurement. With the swab test (figure 1a， 1b)， on the other hand，previously defined risk locations， such asrecesses， welding seams， obstacles， are purposefully sampled by using e.g. cotton swabs. Theswab material is moistened and rinsed with ultrapure water before and during the sampling； thesampling area， usually limited using a template (normally approx. 100 cm²) is wiped in layers andthen eluted with ultrapure water， topped up to a fixed volume of e.g. 50 ml and measured. Figure 1a： Figure： 1b A special procedure in the swab method consists of the use of inorganic fiber materials (e.g. quartzfleece) to wipe the equipment surfaces followed by direct high temperature incineration for TOCdetection. A problem in this procedure is to actually quantify the surface contamination using amoist swab and a dry swab for after-wiping and the use of swab materials with a consistently smallTOC blank value. It must also be emphasized that this procedure only returns one measured valuefor each sampled area， because the swab can only be incinerated once for the TOC measurement，and an increased number of sampling areas might need to be defined. The particular advantage of aqueous rinse samples or swab eluates is that both types of samplescan be processed in a single TOC device using the same measuring method and that additionalsummation parameters can also be detected (pH， conductivity...). Important in this case is alwaysthe measurement and consideration of the blank value of the ultrapure water used in the rinse andthe swab elution， and in the swab the blank value of the swab material. Use of the Multi N/C pharma UV in cleaning validation The multi N/C pharma UV (figure 2) is ideally suited for this TOC analysis due to its very lowdetection limit of 2 ppb and large measuring range of 0 to 10.000 ppb. TOC digestion in this measuring instrument is by way of UV radiation with wavelengths of 185 nm(hard UV radiation) and 254 nm. If necessary， a preoxodisulfate solution can be added to the UVreactor as an oxidation aid. The operating temperature of the UV reactor is at 70-80 C， with thesample flowing directly around the radiation source， ensuring a maximum radiation yield. Theanalyzer operates using a flow injection system and can achieve injection volumes of 0.05 to 20ml. Figure 2： multi N/C pharma UV The following calibration and measuring graphs demonstrate the excellent suitability of themulti N/C pharma UV for the TOC measurement in cleaning validation： Figure 3： Calibration and detection limits Nr. FE (NPOC) c(NPOC) 1 751，4 73，47pg/l 2 782，4 75，31pg/l 3 775，1 74，88pg/l Figure 4： Multi-point calibration using a standard of 600 uag/l TOC at constant concentration by varying the injection volume Figure 5： Measuring an ultrapure water sample with the multi N/C pharma UV (Bild 5) If the parameter TN， is also of interest during the cleaning validation， the multi N/C pharma HT canbe of service. This TOC/TNb analyzer operates in accordance with the principle of catalytic hightemperature incineration and permits the simultaneous detection of TOC and TN， by coupling to achemiluminescence detector for NO detection. Printout and further use permitted with reference to the source. C 2011 Analytik Jena AG Publisher：Analytik Jena AG07745 JenaKonrad-Zuse-StraBe 1 Telephone +49 (0) 36 41/77-70Fax +49 (0) 36 41/77-9279 www.analytik-jena.com info@analytik-jena.com analytikjena Printout and further use permitted with reference to the source. C2009 Analytik Jena AG Publisher：Analytik Jena AGKonrad-Zuse-StraBe 107745 Jena www.analytik-jena.cominfo@analytik-jena.com TOC analysis in cleaning validation and product control within the pharmaceutical industry -Use of the multi N/C pharma /Lit： SP TOC e|NRE