Minimum, analysis time, optimized

Weyland et al. [560,561] used this method to optimize ternary mobile phase compositions for the separation of sulfonamides by RPLC. They fitted the retention surfaces to a quadratic model similar to eqn.(3.39), and also used a combination of a threshold resolution and minimum analysis time (min tm fl / vmin> 1.25 eqn.4.24) [560]. This criterion may yield a good optimum if the optimization is performed on the final analytical column (see table 4.11). 

A considerable amount of work has been published on optimizing the experimental conditions for minimum analysis time under various constraints [52]. One complication arises from the definition of reduced mobile-phase velocity. The actual mobile-phase velocity depends largely on the molecular-diffusion coefficient of the analyte. Thus, very small particles can be used for the analysis of high molecular mass compounds, which have low values. The actual flow rate required will remain compatible with pressure constraints despite the resulting high pneumatic or hydraulic resistance. Detailed results obviously depend greatly on the mode of chromatography used. 

ChromSword is a software tool that is able to find the optimum conditions for H P LC automatically. Most optimizations may be achieved overnight or in weekend nms, resulting in a substantial reduction in working time and effort compared to that normally involved in method development Since the system offers several different isocratic and gradient optimum solutions, the user can select the solution which fits best for his or her particular application. The system optimizes for optimum peak resolution in minimum analysis time. Minimization of the nm time of routine methods offers the potential to substantially increase throughput and productivity in the analytical laboratory. The program also makes complex HPLC method development accessible to those with little HPLC experience. 

Therefore we shall optimize the experimental conditions by looking for the minimum pressure at constant analysis time and efficiency for a given solute pair. It has been shown that this goal is accomplished when the column is operated at the optimum flowrate at which the plate height is minimum (19). The particle size and column length then depend on the plate number and the required analysis time. 

Figure 5 shows that here is a minimum in the analysis time at a separation ratio of about 1.06. Now, from the theory of analytical column design, It would be expected that, if the column was fully optimized, the analysis time would decrease continuously as the separation ratio of the critical pair increased. The reason that a minimum exists in figure 5 arises from the limitations place on the column by the minimum aspect ratio of unity and... 

In contrast to the minor difference in the minimum resolution, however, the difference in the analysis time for the two optimized separations (Figures 6 and 10) was significant The 30% shorter analysis time of 27 min for the optimized density/temperature method compared to 37 min for the density-only optimization clearly demonstrates the superiority of multiparameter optimization strategies. Had the arbitrarily selected temperature of 80°C (2.83 10 3 K l) not been relatively close to the true optimum temperature of 104 °C (2.65 10 3 K"l), the difference would have been even more dramatic ... 

The required analysis time itself appears to be both a logical and an elegant choice for an optimization criterion. Either fne can be minimized, or, for reasons of consistency, l//ne can be maximized. The criterion of minimum required analysis time then corresponds to a constant value for C in eqn.(4.37) ... 

The desired analysis time (fmax) was set equal to 4 min., whereas the value of the minimum time (tmin, which is irrelevant for the optimization process see section 4.4.2) was taken to be 1.5 min. 

It can be seen in the chromatogram of figure 6.11 that four peaks (the three antioxidants plus an unknown impurity) are amply resolved to the baseline. This implies that all values for the peak-valley ratio P are equal to 1 and that the criterion has become very insensitive to (minor) variations in the resolution between the different peak pairs. In the area of the parameter space in which four well-resolved peaks are observed, the only remaining aim of the optimization procedure is to approach the desired analysis time of 4 minutes. The irrelevance of the minimum time tmin is illustrated by the occurrence of the first peak in figure 4.9 well within the value of 1.5 min chosen for this parameter. 

Identifying the worst-case condition was less clear-cut in this example than in the example presented in Section V.B. The worst-case disturbance combination varied with the process design and disturbance type considered. Using the optimization formulation from Section II.B.2 to identify the worst-case was therefore very useful. The preliminary control analysis is sufficient to eliminate most design options, indicating the need to use two tanks despite the fact that this implies unusually low minimum residence times (1 minute compared to the norm of at least 3 minutes) and indicating the need for ratio control of reagent addition. 

Ca(0H)2 added to the PFR was optimized along with the reactor volumes and found to have an optimum value of about 94.5%. Requiring the two tanks to be of equal size did not significantly alter the minimum residence time. Equalsized tanks were therefore assumed for further analysis, as this has inherent benefits in terms of cost and should be optimal for control. 

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