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January 15, 2009 (Vol. 29, No. 2)

Online Monitoring of In-Process Samples

Waters Applies Its UPLC Technology to Obtain QC Results on the Biomanufacturing Floor

  • Putting UPLC to the Test

    Click Image To Enlarge +
    Figure 1. Quantification of the API and process impurities for select aliquots

    Monitoring and quantifying all the components in a process reactor during a synthesis reaction enables the highest quality and yield of the target compound. The real-time monitoring capabilities of the Patrol UPLC Process Analyzer combined with Empower™ 2 Chromatography Data Software can analyze and graphically represent the amounts of identified components in the reactor to make decisions on reaction progress and forward process.

    In a feasibility study conducted by Waters, process application specialists using the Patrol UPLC Process Analyzer monitored the conversion of acetylsalicylic acid to salicylic acid. Aliquots were automatically taken from the reactor vessel at repeated intervals and analyzed with the Patrol UPLC Process Analyzer as the reaction progressed.

    The analyzer baseline-resolved all the components in each aliquot in two minutes with an injection-to-injection cycle time of four minutes (Figure 1). As the reaction progressed the consumption of the starting material and the formation of the API, intermediates, and impurities were monitored and quantified.

    The Patrol UPLC Process Analyzer features a wide linear dynamic range that allows for the simultaneous quantification of both high- and low-level components within the same chromatographic run (Figure 2) even at levels below 0.01% of the major components.

    Online spectroscopic sensors cannot simultaneously quantify such a complex matrix with such varying concentrations. By plotting the %Area of each of the components  in the chromatograms, a map of the reaction can be generated (Figure 3).  This reaction map can be used to determine the optimal time to quench the reaction based upon maximum yield of the API or even minimum formation of the specific low-level impurity.

    With the Patrol UPLC Process Analyzer, manufacturers of biopharmaceutical and pharmaceutical products have a new tool for PAT. Just as LC is today’s gold standard for QC labs, bringing this technology to the manufacturing floor holds tremendous potential for realizing gains in the efficiency of the manufacturing process and the quality of manufactured products in number of ways.

    To better insure that tactical and strategic objectives are met, quality control, PAT, and Six Sigma teams must work closely with their vendors and consultants. The solution chosen for PAT analysis should be thoughtfully designed and built for the purpose of at-line or in-process analysis.

  • Click Image To Enlarge +
    Figure 2. Quantification of both high- and low-level components within the same chromatographic run at levels below 0.01% of the major components
  • Click Image To Enlarge +
    Figure 3. A summary plot for Area % of each component in the reaction vessel for determination of the reaction endpoint

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