Chromatography systems cleaning

The cleaning of process-scale chromatography systems used in the purification of biopharmaceuticals can also present challenges. Although such systems are disassembled periodically, this is not routinely undertaken after each production run. CIP protocols must thus be applied periodically to such systems. The level and frequency of CIP undertaken will depend largely on the level and type of contaminants present in the product-stream applied. Columns used during the earlier stages of purification may require more frequent attention than systems used as a final clean-up step of a nearly pure protein product. While each column is flushed with bulfer after each production run, a full-scale CIP procedure may be required only after every 3-10 column runs. Most of the contaminants present in such columns are acquired from these previous production runs. 

Hayakawa K, Noji K, Tang N, Toriba A, Kizu R, Sakai S, Matsumoto Y. A high-performance liquid chromatography system equipped with on-line reducer, clean-up and concentrator columns for determination of trace levels of nitropolycyclic aromatic hydrocarbons in airborne particulates. Anal Chim Acta 2001 445 205-12. 

A method which uses supercritical fluid/solid phase extraction/supercritical fluid chromatography (SE/SPE/SEC) has been developed for the analysis of trace constituents in complex matrices (67). By using this technique, extraction and clean-up are accomplished in one step using unmodified SC CO2. This step is monitored by a photodiode-array detector which allows fractionation. Eigure 10.14 shows a schematic representation of the SE/SPE/SEC set-up. This system allowed selective retention of the sample matrices while eluting and depositing the analytes of interest in the cryogenic trap. Application to the analysis of pesticides from lipid sample matrices have been reported. In this case, the lipids were completely separated from the pesticides. 

The most common (off-line) sample preparation procedures after protein precipitation are solid phase extraction and liquid-liquid extraction. Multiple vendors and available chemistries utilize 96-well plates for solid phase extraction systems and liquid-liquid extraction procedures. Both extraction process can prepare samples for HPLC/MS/MS assay. Jemal et al.110 compared liquid-liquid extraction in a 96-well plate to semi-automated solid phase extraction in a 96-well plate for a carboxylic acid containing analyte in a human plasma matrix and reported that both clean-up procedures worked well. Yang et al.111 112 described two validated methods for compounds in plasma using semi-automated 96-well plate solid phase extraction procedures. Zimmer et al.113 compared solid phase extraction and liquid-liquid extraction to a turbulent flow chromatography clean-up for two test compounds in plasma all three clean-up approaches led to HPLC/MS/MS assays that met GLP requirements. 

Chemiluminescent immunoassay systems, commercial, 14 151 Chemineer CD6 agitator, 1 739 Chemineer CD6 impeller, 16 673, 701, 703 Chemisorbed water, 23 71 Chemisorption, 1 583-584 for indoor air cleaning, 1 834 parameters of physical adsorption and chemisorption contrasted, l 583t Chemisorption chromatography, 6 405 Chemistry. See also Combinatorial... 

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