Online analytical measurements

Despite the fact that near infrared spectroscopy (NIR) has been used industrially for decades [36], there has been hesitance to accept and trust new process analytical measurement technologies as equivalent or superior to traditional methods. For example, when a discrepancy between online NIR and laboratory analyses is observed, it is rare that the destructive reference methods are ever targeted as the source of error, despite the fact that NIR is often the more precise method. The hesitance to trust more advanced, multivariate tools (which are perhaps less directly understood) has certainly been a detriment to progress in deploying PAT. 

Eurachem (2000). Eurachem Guide Quantifying Uncertainty in Analytical Measurement, 2nd edn. [Online] available http //www.eumchem.iil.pt/guides/QUAM2000-l.pdf [28 February 2007]. 

Automated methods are clearly favored where there are large numbers of samples to be analyzed, when the unit processes such as digestion or separation are slow, and where the analytical measurements must be made online and unattended. 

Hydride mode enables online, batch-mode hydride generation for elements forming volatile hydrides such as arsenic, selenium, and antimony. This step is also performed and the analyte measured during the preconcentration loading/washing step, so it does not add time to the analysis. 

Although batch processes are the workhorse in research laboratory environments, continuous (and semicontinuous) reactors predominate for commercial PE production. In a continuous polymerization reactor, all monomers and reagents are constantly fed into the reactor, and the polymer is isolated from the effluent. Flows are adjusted to achieve the desired steady-state conditions as measured by online analytical instruments and polymer analysis. 

The development of rapid, accurate, and noninvasive online measurement sensors and instraments is a high-priority goal in the commercialization of biotechnology (Figure 3.4). Some of these instraments will build on analytical methods now used in catalysis and other surface sciences, such as... 

Koal et al. (2004) measured four immunosuppressants (cyclosporine A, tacrolimus, sirolimus, and everolimus) in whole blood samples from transplant recipients. The samples were treated first with a protein precipitation step. The supernatant was extracted with a Poros Rl/20 perfusion column (30 x 2.1 mm, 20 tm, Applied Biosystems, Darmstadt, Germany) online. A Luna phenyl hexyl column (2 x 50 mm, Phenomenex, Schaffenburg, Germany) was used for separation. The total run time was 2.5 min. The lower limit of quantitation was 10 ng/mL for cyclosporine A and 1 ng/mL for the other three analytes. 

Gundersen and Blomhoff (1999) used online dilution with online SPE to measure vitamin A (retinol) and other active retinoids in animal plasma. The intention of online dilution in this application was on optimizing SPE extraction conditions rather than on peak focusing during analytical separation. An SPE cartridge packed with Bondapak C18 materials (37 to 53 jt/M, 300 A, Waters, Milford, Massachusetts) and a reversed-phase analytical column (250 x 2.1 mm inner diameter, Superlex pkb-100, Supelco, Bellefonte, Pennsylvania) were controlled by a six-port switching valve (Rheodyne, Cotati,... 

The application from van der Hoeven et al. (1997) used an ADS cartridge online SPE to measure cortisol and prednisolone in plasma and arachidonic acid in urine. A precolumn packed with a C18 alkyl-diol support (LiChrosphere RP-18 ADS, 25 /an, Merck) was used. To reduce run time, column switching was programmed as heart-cut , diverting only the analyte fraction into the analytical column. Another LiChrosphere column (125 x 4 mm inner diameter, Merck) handled separation. After the injection of 100 fiL plasma, the lower limit of detection for prednisolone was 1 ng/mL while cortisol was readily quantitated at its endogenous level of 100 ng/mL. The run time was 5 min. For arachidonic acid, a Hypersil ODS column (200 x 3.0 mm inner diameter, 5 /.an) was used. The injection volume was 200 //I. and run time was 9.5 min. The detection limit was 1 ng/mL and recovery was 77%. 

Another approach is increasing throughput via a monolith analytical column. Vintiloiu et al. (2005) used a self-made RAM online SPE under turbulent flow conditions to measure rofecoxib, a cyclooxygenase-2 inhibitor, in rat plasma. They constructed a cartridge (0.76 x 50 mm) packed with LiChrosphere 60 RP-18 ADS particles (40 to 63 /an, Merck KgaA). The analytical column was a Chromolith Speed ROD (RP-18, 50 x 4.6 mm, Merck KgaA). The injection volume was... 

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