The determination of propylthiouracil in urine with 2:6-dichloro-quinonechloroimide.

Previous colorimetric methods for the determination of antithyroid compounds of the thiouracil type have been based upon the bluish-green colour which is given when compounds containing the C=S group react with Grote's (1931) reagent. Methods for the determination of thiouracil levels in urine using this reaction have been described by Anderson (1944), Williams, Jandorf, and Kay (1944), Chesley (1944), Christensen (1945), Paschkis, Cantarow, Rakoff, and Tillson (1945), and others. With the exception of Williams et al. (1944), all of these workers have reported on the instability of the stock Grote reagent, which necessitates not only the frequent preparation of fresh reagent, but also the inclusion of standards with each set of unknowns. The method of Williams and his colleagues, however, has the disadvantage of a 12-hour digestion procedure and the inconvenient adjustment of the reaction with a strong base. Recently Olson, Ely, and Reineke (1947) have claimed to have produced a stable Grote reagent by the application of a suitable ageing process. Since the method described here for the colorimetric determination of propylthiouracil involves a new colour reaction, it is not necessary to review further previous work. A new colour reaction for antithyroid drugs of the thiouracil type has already been described (McAllister, 1950). This is based upon the reaction of the compound in a buffer at pH 8.0 with 2: 6-dichloroquinone-chloroimide to give a yellow chloroform-soluble complex. This colour reaction has also been shown to be specific for the newer antithyroid compounds of the mercaptoimidazole type (McAllister, 1951a), and has been applied on a quantitative basis to the determination of methylthiouracil in urine (McAllister, 1951b). In applying this colour reaction to the determination of propylthiouracil in urine, certain improvements have been introduced, the most important of these being a preliminary ether extraction of the compound from the urine at pH 6.0.