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Differenzierende TOC-Bestimmung zur Charakterisierung von Reinstwasser und Rückstandsprüfung im Verlauf der Reinigungsvalidierung

Wolfgang Woiwode a und Stefan Huber b

TECHPharm Woiwode GmbH a und DOC-Labor Huber b , Karlsruhe

Differentiating Organic Carbon Analysis for Characterization of Purified Water and Identification and Quantification of Residues in Aqueous Rinses from Cleaning Validation Determination of Total Organic Carbon (TOC) is a pharmacopoeial, commonly accepted method for global quantification of dissolved organic residues in water. By means of Liquid Chromatography in a solely aqueous system and applying a carbon-selective detector operating continuously, differentiation, identification and quantification of organic compounds representing TOC of a given sample became feasible. Proceeding in this manner, one major disadvantage of the global TOC-parameter, namely the lack of information about individual compounds, definitely was eliminated. This highly specific method now for the first time was introduced into pharmaceutical industry. Chromatograms taken at different steps of water treatment clearly reflect full performance of water systems during Installation Qualification and Performance Qualification. In case of malfunction, comparison of the current with the initial chromatograms allows straight-forward problem solving and identification of possible contaminants. An almost unique opportunity represents investigation of post final rinses during cleaning validation: differentiation of active ingredients, inactive ingredients, cleaning agents and contaminants in principal can be performed in a single rund down to the ppb-level. Similarly, aqueous samples taken from premises and equipment can be monitored more efficiently in respect of organic residues. More general differentiating organic carbon analysis allows identification and quantification, or exclusion of compounds and contaminants from any aqueous rinse. Examples, results and concepts of cleaning validation together with obvious limitations of this method are discussed in more detail.

Key words Fingerprint · Gesamtkohlenstoff · Kohlenstoffdetektor · Kontamination · LC/OCD · Post Final Rinse · Reinigungsvalidierung · TOC-differenziert · TOC-gesamt · Wasseruntersuchungen