Solvent consumption

The solvent consumption is simply obtained by multiplying the analysis time by the optimum flow rate as shown below. 

The solvent consumption appears to be in conflict with the corresponding optimum flow rates. Substances with high (a) values have a very high optimum flow rate (over 11 per min. for (a=1.2) and the column diameter is over 6 mm which would indicate a very large solvent consumption. However, because the separation is simple, a very rapid separation is achieved with analysis times of less than a second. As a consequence, only a few ml of solvent is necessary to complete the analysis. The apparatus, however, must be designed with an exceedingly fast response and very special sample valves would be necessary. In contrast, a very 

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The solvent consumption (Vsoi)is equal to the product of the analysis time and the optimum flow rate, 

Substituting for (Tmin) from equation (4) and for (Q0pt) from equation (15), 

It is seen from equation (18) that the solvent consumption is directly proportional to the charge placed on the column and the capacity ratios of the first peak of the critical pair and the last eluted peak respectively. It is also seen that, as with the optimized analytical column, the diffusivity of the solute and the viscosity of the mobile phase play no part in controlling the solvent economy, it should be pointed out, however, that this is only true for a completely optimized column 

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On considering the solvent consumption and waste generation, it is clear that NIR measurements reduce drastically the amount of CH CN consumed compared with the HPLC procedure. On the other hand, the sample frequency obtained by the NIR methodology was higher than those obtained by HPLC. 

The analysis must be completed with the minimum solvent consumption. 

The maximum and minimum flow rate available from the solvent pump may also, under certain circumstances, determine the minimum or maximum column diameter that can be employed. As a consequence, limits will be placed on the mass sensitivity of the chromatographic system as well as the solvent consumption. Almost all commercially available LC solvent pumps, however, have a flow rate range that will include all optimum flow rates that are likely to be required in analytical chromatography... 

Another critical instrument specification is the total extra-column dispersion. The subject of extra-column dispersion has already been discussed in chapter 9. It has been shown that the extra-column dispersion determines the minimum column radius and, thus, both the solvent consumption per analysis and the mass sensitivity of the overall chromatographic system. The overall extra-column variance, therefore, must be known and quantitatively specified. 

The optimum mobile phase velocity will also be determined in the above calculations together with the minimum radius to achieve minimum solvent consumption and maximum mass sensitivity. The column specifications and operating conditions are summarized in Table 4. 

There remains the need to obtain expressions for the optimum column radius (r(opt)), the optimum flow rate (Q(opt)), the maximum solvent consumption (S(sol)) and the maximum sample volume (v(sam))-... 

The minimum solvent consumption will be obtained from the product of the optimum flow rate and the analysis time. 

The amount of gas employed in a GC analysis is not usually important, particularly where open tubular columns are used. In LC, however, solvent use presupposes a solvent disposal difficulty if not a toxicity problem and, thus, solvent consumption can be extremely important. 

Figure 9. Graph of Solvent Consumption against the Separation Ratio of the Critical Pair...

It follows from equation (2) that the sample load will increase as the square of the column radius and thus the column radius is the major factor that controls productivity. Unfortunately, increasing the column radius will also increase the volume flow rate and thus the consumption of solvent. However, both the sample load and the mobile phase flow rate increases as the square of the radius, and so the solvent consumption per unit mass of product will remain the same. 

Generally, size exclusion chromatography is carried out using columns with an internal diameter of 7.8 mm. However, some SEC applications require the use of expensive solvents. For this purpose, size exclusion columns with a smaller internal diameter (4.6 mm) have been developed. Of course one should use proportionally lower flow rates with narrow-bore columns. If the standard column size uses a flow rate of 1 ml/min, then the smaller 4.6-mm columns should be used at a flow rate of 0.35 ml/min. This provides the same linear velocity as 1 ml/min on 7.8-mm columns. The decreased flow rate reduces solvent consumption and solvent disposal cost. The performance of the smaller diameter columns is not compromised if properly optimized instrumentation is used. 

Narrow-bore columns are most useful for the analysis of polymers that are difficult to analyze in inexpensive solvents. However, if the appropriate equipment is available, good results can be obtained for a broad range of standard analyses. A comparison of an analysis of standards between an equivalent bank of conventional 7.8-mm and solvent efficient 4.6-mm columns is shown in Fig. 11.4. The columns used were Styragel HR 0.5, 1, 2, and 3 columns at 35°C with tetrahydrofuran (THF) as the solvent. The flow rate was 1 ml/min for the conventional columns (Fig. 11.4A) and 0.35 ml/min for the solvent-efficient 4.6-mm columns (Fig. 11.4B). If the correct equipment is available, the reduced solvent consumption of these solvent-efficient Styragel columns is of value to the environmentally conscious user. 

Conventionally, analytical SEC columns have been produced with an internal diameter of 7.5 mm and column lengths of 300 and 600 mm. In recent years environmental and safety issues have led to concerns over the reduction of organic solvent consumption, which has resulted in the development of columns for organic SEC that are more solvent efficient (13). By reducing the internal diameter of the column, the volumetric flow rate must be reduced in order to maintain the same linear velocity through the column. This reduction is carried out in the ratio of the cross sectional areas (or internal diameters) of the two columns. Eor example, if a 7.5-mm i.d. column operates at 1.0 ml/min, then in order to maintain the same linear velocity through a 4.6-mm i.d. column the flow rate would be... 

Since the first separation of enantiomers by SMB chromatography, described in 1992 [95], the technique has been shown to be a perfect alternative for preparative chiral resolutions [10, 21, 96, 97]. Although the initial investment in the instrumentation is quite high - and often prohibitive for small companies - the savings in solvent consumption and human power, as well as the increase in productivity, result in reduced production costs [21, 94, 98]. Therefore, the technique would be specially suitable when large-scale productions (>100 g) of pure enantiomers are needed. Despite the fact that SMB can produce enantiomers at very high enantiomeric excesses, it is sometimes convenient to couple it with another separation... 

As a matter of fact, the main advantage in comparison with HPLC is the reduction of solvent consumption, which is limited to the organic modifiers, and that will be nonexistent when no modifier is used. Usually, one of the drawbacks of HPLC applied at large scale is that the product must be recovered from dilute solution and the solvent recycled in order to make the process less expensive. In that sense, SFC can be advantageous because it requires fewer manipulations of the sample after the chromatographic process. This facilitates recovery of the products after the separation. Although SFC is usually superior to HPLC with respect to enantioselectivity, efficiency and time of analysis [136], its use is limited to compounds which are soluble in nonpolar solvents (carbon dioxide, CO,). This represents a major drawback, as many of the chemical and pharmaceutical products of interest are relatively polar. 

The cyclic steady state SMB performance is characterized by four parameters purity, recovery, solvent consumption, and adsorbent productivity. Extract (raffinate) purity is the ratio between the concentration of the more retained component (less retained) and the total concentration of the two species in the extract (raffinate). The recovery is the amount of the target species obtained in the desired product stream per total amount of the same species fed into the system. Solvent consumption is the total amount of solvent used (in eluent and feed) per unit of racemic amount treated. Productivity is the amount of racemic mixture treated per volume of adsorbent bed and per unit of time. 

The equivalent TMB operating conditions and model parameters for the reference case were given in Table 9-1 and Fig. 9-9 presents the corresponding steady state internal concentration profdes obtained with the simulation package. The extract and raffinate purities were 97.6 % and 99.3 %, respectively the recoveries were 99.3 % and 97.6 % for the extract and raffinate streams. The solvent consumption was 1.19 L g and the productivity was 68.2 g/day - L of bed. 

The vertex of a separation region points out the better operating conditions, since it is the point where the purity criteria are fulfilled with a higher feed flow rate (and so lower eluent flow rate). Hence, in the operating conditions specified by the vertex point, both solvent consumption and adsorbent productivity are optimized. Comparing the vertex points obtained for the two values of mass transfer coefficient, we conclude that the mass transfer resistance influences the better SMB operating conditions. Moreover, this influence is emphasized when a higher purity requirement is desired [28]. 

At the current time, there is considerable interest in the preparative applications of liquid chromatography. In order to enhance the chromatographic process, attention is now focused on the choice of the operating mode [22]. SMB offers an alternative to classical processes (batch elution chromatography) in order to minimize solvent consumption and to maximize productivity where expensive stationary phases are used. 

Packed column SFC has also been applied to preparative-scale separations [42], In comparison to preparative LC, SFC offers reduced solvent consumption and easier product recovery [43]. Whatley [44] described the preparative-scale resolution of potassium channel blockers. Increased resolution in SFC improved peak symmetry and allowed higher sample throughput when compared to LC. The enhanced resolution obtained in SFC also increases the enantiomeric purity of the fractions collected. Currently, the major obstacle to widespread use of preparative SFC has been the cost and complexity of the instrumentation. 

Little has been said concerning the column diameter which, unfortunately, is an aspect of column technology that involves extensive theoretical discussion which is probably not appropriate here. Each column that is optimized to analyze a particular sample in the minimum time and with the minimum solvent consumption will also have an optimum diameter. The optimum column diameter... 

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