Loadability for Poor Solubilities

Although high solubility should be preferred for good productivities, time pressure and thermodynamics can require the acceptance of poor solubilities. Nearly half of R D laboratories involved in preparative chromatography examine 10-100 samples per day and the number of candidates for preparative separation is still increasing (Neue ef al., 2003). Obviously, time and large amounts of sample can not be spent for systematic evaluations and tedious solubility studies. Very often the amount of sample is also too small to carry out extensive experiments. 

Cases of severe solubility limitations ( 5gl ) are handled in different ways. First, the sample may be dissolved in a solvent different from the mobile phase, for example, the sample solvent may be 100% organic and quite different from the mobile phase. In most cases, this solvent is, in addition to its high solubility, also a much stronger chromatographic solvent than the mobile phase. In such a case, large sample injections into the mobile phase may have an adverse effect on the 

Peak distortion and precipitation problems due to injection of solvents of high solubility can be defused by changing the injection technique. The right-hand part 

Another method for separating low-solubility samples, which is well known in the downstream processing of biopolymers, starts with a large volume of sample dissolved in a chromatographically weak solvent. This solution is fed to the column. As the solute has a relatively strong affinity to the stationary phase, for example, silica, it is adsorbed and concentrated at the column inlet. This has the effect of introducing the sample as a concentrated plug. 

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