The separation of polar, low molecular weight, water-soluble compounds from specimens prior to quantitation has long been a problem in analytical toxicology. Others have successfully used in situ derivatization, prior to extraction, to resolve this problem (1,3). An application of the Schotten-Baumann reaction leading to a simple extraction of tris(hydroxymethyl)aminomethane (THAM) followed by HPLC is presented. This may be a generic approach to the analysis of other polyhydroxy, water-soluble compounds.