Programmed selectivity optimization

To achieve this goal, method developers should ideally find themselves in the opposite situation, being equipped with flexible, advanced instrumentation, including a variety of possible injectors and detectors, facilities for temperature or solvent programming, etc.. Multichannel detectors are very useful, as they may be of assistance in recognizing the different sample components when they move about in the chromatogram during the selectivity optimization process (section 5.6). 

Resolution in programmed temperature GC is enhanced if the programming rate (rr/F) is decreased and if the initial temperature (T) is decreased. Giddings [606] suggested that the first peak in a programmed analysis should not appear within about five times the hold-up volume of the column. Since the temperature has little effect on the selectivity in GC (see section 3.1.1), the optimization of temperature programs is a process that may be seen as resolution optimization rather than as selectivity optimization. 

If the program is optimized so that all sample components are eluted under optimal conditions, then other (secondary) parameters may be used for the optimization of the selectivity. However, changes in the secondary parameters may imply that the parameters of the program need to be re-optimized. For example, if the selectivity in a temperature programmed GC analysis is insufficient, then another stationary phase may be used to enhance the separation. However, the optimum program parameters obtained with one stationary phase cannot be transferred to another column that contains another stationary phase. The re-optimization of the temperature program for the other column will require at least one additional experiment to be performed. 

Selectivity optimization of simple, continuous gradients will be easier than the optimization of complex multisegment programs, because there are bound to be serious... 

Because this optimization only concerned program parameters and not selectivity parameters, the response surface will have been relatively simple. Therefore, the probability that the Simplex procedure would arrive at the global optimum rather than at a local one was greater than it was in section 5.3, where we described the use of the Simplex method for selectivity optimization. 

The response surface for the optimization of the primary (program) parameters in programmed temperature GC is less convoluted than a typical response surface obtained in selectivity optimization procedures (see section 5.1). This will increase the possibility of a Simplex procedure locating the global optimum. 

However, the calculations required for such an optimization are quite involved. This is caused by the requirement to calculate the retention times of each solute (and the resolutions of each pair of adjacent peaks) from the isocratic retention vs. composition relationships. In order to characterize the response surface, these calculations need to be performed a number of times. Finally, the optimum needs to be found on the response surface. If all four program parameters (initial and final concentration, slope and shape) are considered, the number of calculations would be large, even though the response surface may be simple compared with those encountered in selectivity optimization (see the discussion in section 6.3.2.1). 

The Sentinel method is the outstanding exponent of the group of interpretive methods, as it has already been applied successfully for selectivity optimization in programmed solvent LC. However, other interpretive methods, based either on fixed experimental designs or on iterative procedures, can be applied along the same lines. It was seen in section 6.3.2.3 that the extension of the Sentinel method to incorporate gradient optimization was fairly straightforward. 

This type of optimization is a nonlinear programming (NLP) problem, which can be performed automatically in Aspen Plus. Click Model Analysis Tools on the Data Browser window and select Optimization. Click the New button and then OK to create an ID. The window shown in Figure 4.3 opens, which has a number of page tabs. 

Optimize for Highly similar sequences by choosing the megablast option under the Program Selection section. 

Retention time is also strongly influenced by the choice of stationary phase. Several factors must be taken into account when selecting a column for separating androgens. Retention time and resolution will be affected by the choice of column length, stationary film thickness and polarity, and the temperature program rate. The programmed temperature optimization of a mixture of anabolic... 

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