Solvent reaction product artifacts

Figure 1.6 presents an example for the formation of a reaction product on the surface of a sorbent. The result of a solvent extraction of activated charcoal with CS2 and CS2/methanol, respectively, shows quite different artifact formation after a 48-hour storage period. Four new compounds could be found in the sample containing methanol as a desorption agent. All of them could be identified as substances formed by the reaction of CS2 and methanol in the presence of activated charcoal. 

Moreover, nitrones can be generated from N-hydroxy products during extraction into an organic solvent, such as diethyl ether. The latter contains acetaldehyde as an impurity even after careful distillation. Indeed, nitrones arising as artifacts from the reaction of primary hydroxylamines, metabolically derived from methamphetamine and chlorpromazine, with acetaldehyde upon sample treatment with ether have been identified23,39. Acetone is frequently used as one of the components of the solvent systems applied for TLC analysis. 

A comparison of LC methods for determination of cis-trans isomers of P-carotene was made on Vydac C18 201 TP and calcium hydroxide columns (186). The purity and relative distribution of P-carotene and its isomers in several commercially available products were evaluated by HPLC on several columns using a mobile phase of methanol/water (97 3) (187). Because carotenoids and chlorophylls are very sensitive to the nature of injection solvent, such as acetone, sample-solvent interaction may give rise to distorted and even false peaks (188). Because metal column frits may damage carotenoids. Teflon column frits should be used (189). Also artifacts may be produced on the column by reactions among the carotenoids, injection solvents, and mobile phase. Losses that occur during extraction and saponification can be reduced by use of suitable antioxidants (189). 

Schemes for combinatorial syntheses of compounds, particularly candidate pharmaceuticals, now attract great interest because of the potential for greatly speeding up the discovery of new drug molecules. They are based on carrying out chemical reactions on solid artifacts, the starting material, intermediates and final product being attached to the solid phase on completion the product is cleaved away into solution. Typically the solid substrate is a mass of small (of the order of tens or 100 pm or so) porous beads made of polymer or silica resin. They are suspended, by agitation, in reactant solution, which is removed on completion by filtration. The beads are washed with solvent between stages of synthesis.

---