Fluorouracil solution

Efudex solution consists of 2% or 5% fluorouracil on a weight/weight basis, compounded with propylene glycol, 

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Fluorouracil was relatively stable in PVC containers compared with glass, but this depends on concentration and storage temperature. Fluorouracil solutions are incompatible with synthetic elastomers containing packaging and infusion materials.218,219... 

An amount of enzyme preparation equivalent to 900 mg of wet cells was made up to 25 ml with the above potassium phosphate buffer solution. 150 mg (1.15 mmol) of 5-fluorouracil and 1.0 gram of thymidine (4.12 mmol) were dissolved in 15 ml of the above potassium phosphate buffer solution. The mixture was incubated at 37°C for 18 hours. After this time, enzyme action was stopped by the addition of four volumes of acetone and one volume of peroxide-free diethyl ether. The precipitated solids were removed by filtration, and the filtrate was evaporated under nitrogen at reduced pressure until substantially all volatile organic solvent had been removed. About 20 ml of aqueous solution, essentially free of organic solvent, remained. This solution was diluted to 100 ml with distilled water. 

A solution of 10.0 grams of purified S-methyl ether of 2-thio-5-fluorouracil, MP 230° to 237°C, in 150 ml of concentrated aqueous hydrochloric acid (containing approximately 37% by weight HCI) was refluxed under nitrogen for 4 hours. The reaction mixture was then evaporated in vacuo. The crystalline brownish residue was recrystallized from water. The resulting recrystallized product was further purified by sublimation in vacuo at 190° to 200°C (bath temperature)/0.1 mm pressure. There was obtained 5-fluorouracil, in the form of colorless or pinkish-tan crystals, MP 282° to 283°C (with decomposition). 

Lawrence et al. [66] in a split face study, compared the efficacy and safety of Jessner s solution and 35% TCA with 5% fluorouracil in the treatment of widespread facial actinic keratoses. Fifteen patients were treated. Both treatments reduced the number of visible actinic keratoses by 75%. Similarly, both caused equivalent reductions in keratinocyte atypia, hyperkeratosis, and parakeratosis. Compared to fluorouracil, only one application of the peel was necessary. 

To explore the feasibility of these polymers as a pendant delivery drug delivery system, 5-fluorouracil activated by 1,1,1,3,3,3-hexamethyl disilazane was coupled to the phosphite via the Todd reaction as shown in Scheme 2. Briefly, the polymer (PPU-7) solution in dimethylacetamide was mixed with a 1 1 v/v solution of carbon tetrachloride and methylene chloride containing 0.5 volume percent of triethylamine (TEA) as catalyst. The activated drug dissolved in methylene chloride was added slowly into the mixture and allowed to react for 48 hours at room temperature. The product was isolated by precipitation into carbon tetrachloride. 

Flucytosine Flucytosine, 5-fluorocytosine (35.4.4), is synthesized from fluorouracil (30.1.3.3). Fluorouracil is reacted with phosphorous oxychloride in dimethylaniline to make 2,4-dichloro-5-fluoropyrimidine (35.4.2), which is reacted with ammonia to make a product substituted with chlorine at the fourth position of the pyrimidine ring—4-amino-2-chloro-5-fluoropyrimidine (35.4.3). Hydrolysis of the chlorovinyl fragment of this compound in a solution of hydrochloric acid gives the desired flucytosine [52-55]. 

Fluoroplex 1% topical solution contains fluorouracil 1%, propylene glycol, sodium hydroxide or hydrochloric acid to adjust the pH, and purified water. 

PCR Incorporated (associated with the Schuman-Tarrant group) manufactures 5-fluorouracil by this process for use in cancer chemotherapy and has had annual sales of over a million dollars for the last several years. This fluorination process, which is selective even above room temperature and may be conducted in H20, CF3C02H, or CF3CH2OH, is a curiosity. The selectivity observed at higher temperatures must involve a strong solvent effect rather than being primarily a feature of the fluorination process itself. A report by Cech and Holz describes the fluorination of nitrogenous bases and associated nucleosides to produce 2 -deoxy-5-fluorouridine derivatives (96). This study requires that a saturated room-temperature solution of molecular fluorine in acetic (or tri-... 

The photoaddition of water to a variety of naturally occurring pyrimidine derivatives has been reported. Photolysis in aqueous solution of uracil (224 R = H), uridine (224 R=ribosyl), and uridylic acid results in the formation of the corresponding 6-hydroxy-5,6-dihydropyrimidine (225)208-210 these structures have been established by independent synthesis.209 Analogous photoadditions have been observed in 1,3-dimethyluracil211 and 5-fluorouracil.212 These additions are reversible. 

Nishimoto S, Hatta H, Ueshima H, Kagiya T (1992) 1-(5 -Fluoro-6 -hydroxy-5, 6 -dihydrouracil-5 -yl)-5-fluorouracil,a novel N(1)-C(5) linked dimer that releases 5-fluorouracil by radiation activation under hypoxic conditions. J Med Chem 35 2711-2712 Norman ROC, Storey PM, West PR (1970) Electron spin resonance studies, part XXV. Reactions of the sulphate radical anion with organic compounds. J Chem Soc (B) 1087-1095 Novais HM, Steenken S (1986) ESR studies of electron and hydrogen adducts of thymine and uracil and their derivatives and of 4,6-dihydroxypyrimidines in aqueous solution. Comparison with data from solid state. The protonation at carbon of the electron adducts. J Am Chem Soc 108 1-6... 

All of the direct fluorinations reported appear to be addition-elimination processes with solvent involvement (Scheme 42). A study of the mechanism and stereochemistry of uracil and cytosine fluorination using fluorine and acetyl hypofluorite has implicated a radical-cation mechanism (86JOC1466). The effect of acetate ion on the products proved to be important. In its absence both m-isomers (49) and trans-isomers (50) were observed in the reaction mixture, but only 50 [and 5-fluorouracil (51)] in its presence. The process has been rationalized in terms of the reaction diagram shown in Scheme 43. NMR studies have revealed that the acetate from the solution containing acetate ion, rather than the residue from acetyl hypofluorite, binds to the 6-position of uracil to form the intermediates (49 and 50). Acetate is a sufficiently strong base to induce trans-elimination of acetic acid from the cis-isomer (49). 5-Fluorouracil (51) was obtained in 45% yield from these reaction sequences (86CJC424). 

Solutions. Wear goggles and protective gloves and clothing. Cover spill with a 1 1 1 mixture by weight of soda ash, clay cat litter (bentonite), and sand. Scoop the mixture into a container and transport to the fume hood. Estimate the weight of fluorouracil in the spilled liquid and add 10% calcium hypochlorite solution (see waste disposal for preparation), allowing 100 mL for each 500 mg of fluorouracil. Allow to stand overnight,... 

Wear goggles and protective gloves and clothing. To each 10 mL of solution containing 500 mg of fluorouracil, add 40 mL of an aqueous solution of calcium hypochlorite (prepared by stirring 10 g of calcium hypochlorite in 100 mL of water for 2 hours, and then removing the undissolved material by filtration). Stir the solution at room temperature for 5 hours, remove the precipitated calcium fluoride by filtration, and discard as normal refuse. Wash the filtrate into the drain with water.3... 

An amount of enzyme preparation equivalent to 900 mg of wet cells was made up to 25 ml with the above potassium phosphate buffer solution. 150 mg (1.15 mmol) of 5-fluorouracil and 1.0 gram of thymidine (4.12 mmol) were dissolved in 15 ml of the above potassium phosphate buffer solution. 

A solution of 10.0 grams of purified S-methyl ether of 2-thio-5-fluorouracil,... 

One process from US Patent 4,107,162 27.4 g of 2,4-bis(trimethylsilyl)-5-fluorouracil and 7.7 g of 2,3-dihydrofuran are dissolved in 70 ml of acetonitrile, and 30 ml of an acetonitrile solution containing 1.3 g of anhydrous stannic chloride are added thereinto with cooling and stirring. 50 ml of acetonitrile containing 1.3 ml of water dissolved therein are then dropwise added over 15 minutes. After return to room temperature, the reaction is further effected with stirring at 40°C for 5 hours. The reaction mixture is neutralized by adding 1 N aqueous ammonia with cooling and... 

Droperidol Droperidol has pH-dependent incompatibility with many drugs. It is not compatible with nafcillin sodium, fluorouracil, folic acid, frusemide, heparin, methotrexate, or barbiturates. Droperidol should not be stored in PVC bags containing intravenous infusions, although some solutions appear to be stable.157... 

Cisplatin Cisplatin is incompatible and should not be mixed with infusions of bisulfite preservatives, sodium bicarbonate, fluorouracil, mannitol and potassium chloride, thiotepa, and aluminum containers. Cisplatin is unstable in sodium chloride solutions and concentrated forms.208,209... 

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