Propylthiouracil methods

Taste. Of the fundamental tastes, bitter is unique in showing human genetic differences in sensitivity. Six decades ago, it was reported tiiat phenylthiocarbamide (PTC) tasted extremely bitter to some individuals while being almost tasteless to others (45). Tlie ability to taste PTC was found to be a dominant genetic trait which occurs across gender, age and culture, with 70% of the American pulation carrying the dominant trait (46). Sensitivity to PTC and propylthiouracil (PROP) are correlated with sensitivities to otiier bitter tasting compounds, such as caffeine, saccharin (after-taste) and salts of i tassium cations and benzoate anions (47,48,49 0). However, in a reexamination of the sensitivity to NaQ and KQ, no differences were found between tasters and nontasters to non-PTC type compounds, and the statistical methods that showed differences were questioned (51). Individuals who do not respond to PTC are not necessarily insensitive to quinine, another intensely bitter compound (49,50,52). 

A more comprehensive approach was reported in 1975 by Brabander and Verbeke (612). In this method, tissue samples were extracted with methanol and the acidified extract defatted with petroleum ether to be loaded onto a Dowex 50W-X8 anion-exchange resin. Following elution with aqueous methanol, the concentrated buffered extract was further defatted with diethyl ether. The sample was derivatized with 7-chloro-4-nitrobenzo-2-oxa-l,3-diazole (NBD-Cl) to be further spotted on a silica high-performance thin-layer chromatographic plate developed in two dimensions using chloroform/ethanol and chloroform/propionic acid consecutively as eluents. Detection of the propylthiouracil, phenylthiouracil, and tapazole residues was carried out on the basis of the fluorescence induction of the NBD derivatives of the drugs with an alkaline cysteine solution. 

The most recent modification of the NBD-Cl method involves a further improvement in its qualitative support (616). It involves the infusion of the extract employed for thin-layer chromatography via an electrospray interface into a mass spectrometer operating in the multiple-stage mass spectrometry mode, thus allowing confirmation of suspect results. The cleanup of the thyroid gland samples was also performed with a selective extraction procedure, based on the specific complex formation of the thiouracil, methylthiouracil, propylthiouracil and phenylthiouracil, tapazole, and mercaptobenzimidazole residues with mercury ions bound in a Dowex 1-X2 affinity column. 

A mercurated affinity column was also employed by Schilt et al. (617) for sample cleanup in a method for the determination of residues of thiouracil, methylthiouracil, and propylthiouracil in cattle urine by gas chromatography and niuogen phosphorous or mass spectrometry detection. The presence of nitrogen... 

Obeidat WM, Price JC. Preparation and in vitro evaluation of propylthiouracil microspheres made of Eudragit RL 100 and cellulose acetate butyrate polymers using the emulsion-solvent evaporation method. Journal of Microencapsulation. May 2005 22(3) 281-289. PubMed PMID 16019914. Epub 2005/07/16. eng. 

The methods used in all of our studies were as follows (Nicholson and Altman, 1972a). Animals were made hypothyroid by daily injection with 0.05 ml of 0.2% propylthiouracil (PTU) in 1% carboxymethyl cellulose on postnatal(P) days 0 (birth)- 10 (PO-10) 0.1 ml 0.2% PTU on Pll-20 and 0.1% 0.4% PTU on P21- 30. Thyroids from these animals were monitored histologically at all ages. Animals were judged to be hypothyroid on the basis of lack of colloid and a hyperplastic follicular epithelium. Hyperthyroid animals were injected with 1 ug L-thyroxine (T4) in 0.1 ml physiological saline on PO-7 2 ug on P8-14 3 ug on P15-21 and 5 ug on P22-30, according to the tolerance schedule devised by Hamburgh et al. (1964). 

Uses Treatment with the thionamides thia-mazole (carbimazole), its active metabolite methimazole, or propylthiouracil remains one of the main therapeutic methods in hyperthyroidism. Unlike treatment with or surgery, thionamides are not ablative and permanent remission rates are low, even after prolonged administration. Suppression of serum thyrotropin (TSH) when antithyroid drugs are discontinued is a poor prognostic indicator of cure [13 ]. In a retrospective study there were higher remission rates at 6,12, and 24 months after withdrawal of antithyroid drugs in 40 subjects who had mild hypothyroidism (serum TSH over 10 pIU/l) compared with 37 sex- and age-matched patients who remained euthyroid during treatment with... 

The addition of sodium acetate is not essential but was found to increase the sharpness of the end-point. This method has been adopted by the B.P for propylthiouracil and methylthiouracil. 

The tablets can be assayed directly by the mercury method given above using a weight of powdered tablets equivalent to about 0 4 g of propylthiouracil. The silver precipitation method, however, is not applicable to the tablets since an interfering red colour completely obscures the endpoint. 

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