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kilomentor | 12 February, 2007 18:06
In Kilomentor’s assessment, the most important analytical paper in the analytical chemical literature in terms of usefulness to process development chemists is almost unknown. George B. Smith and George V. Downing wrote a note called Phase Solubility Analysis as the Basis of a Separation Method [Anal. Chem. 51(13) 2290-2293 (1979).]
In this article the authors describe a purification technique for essentially pure chemical solids called informally in Merck Sharpe & Dohme laboratories “swishing”. Swish purification of several grams or several hundred grams of material is accomplished by overnight equilibration in a suitable solvent (an anti-solvent or very poor solvent actually), with magnetic stirring on a small-scale or with mechanical agitation in a Morton (creased) flask for large quantities. The technique is not readily applicable to small samples. Swishing is actually exhaustive equilibrium trituration.
Separating the trituration liquid from the residual solid results in a highly purified solid phase on the one hand and a solution in which many minor impurities are dramatically concentrated on the other. When thin-layer chromatography (TLC) is used to see the pattern and intensities of the impurities, the combined method is called Swish TLC.
If the solid mixture of impurities and main compound from one swishing is subjected to a second swish purification, the impurities may be even further concentrated, often sufficient to provide samples of one or more impurities, which are often of previously undetermined structure. The technique is a powerful resource to identify and characterize minor impurities, for a Drug Master File, for example.
Very often swish TLC can reveal impurities which by HPLC for example are below the limit if detection.
Swish TLC is also a forensic method by which impurity patterns ca be “fingerprinted” in order to indicate the particular process used to manufacture the sample.
In addition, the method can be useful for examination of process-change samples, process-deviation samples, and stability samples or in any other situation where the great excess of the main component interferes with other separation methods.
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