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Butalbital
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C11H16N2O3 224.26

2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-(2-methylpropyl)-5-(2propenyl)-.
5-Allyl-5-isobutylbarbituric acid [77-26-9].
» Butalbital contains not less than 98.0 percent and not more than 102.0 percent of C11H16N2O3, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Identification—
B: Ultraviolet Absorption 197U—
Solution: 15 µg per mL.
Medium: 0.1 N sodium hydroxide.
Absorptivities at 246 nm, calculated on the dried basis, do not differ by more than 2.5%.
Melting range 741: between 138 and 141.
Loss on drying 731— Dry it in vacuum at room temperature to constant weight: it loses not more than 0.2% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.002%.
Chromatographic purity—
Chloroform-methanol— Mix equal volumes of chloroform and methanol.
Standard preparations— Dissolve a quantity of USP Butalbital RS in Chloroform-methanol to obtain a solution having a concentration of 40 mg per mL (Solution A). Dilute 1.0 mL of Solution A with Chloroform-methanol to 100 mL, and mix (Solution B); mix 5.0 mL of Solution B with 5.0 mL of Chloroform-methanol (Solution C); and mix 5.0 mL of Solution C with 5.0 mL of Chloroform-methanol (Solution D).
Test preparation— Dissolve a quantity of Butalbital in Chloroform-methanol to obtain a solution having a concentration of 40 mg per mL.
Procedure— In a suitable chromatographic chamber, arranged for thin-layer chromatography and lined with filter paper, place a volume of a developing solvent consisting of a mixture of acetone, dichloromethane, methanol, and ammonium hydroxide (50:30:10:10) sufficient to develop the chromatogram. Cover the chamber, and allow it to equilibrate for 30 minutes. Apply 10 µL each of the Test preparation and Solutions A, B, C, and D to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Develop the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and dry the plate in a current of air. Spray the plate with a reagent prepared by dissolving 5 g of potassium hydroxide in a mixture of 25 mL of water and 75 mL of alcohol. Allow the plate to dry in warm air for 10 minutes, and examine the chromatograms under UV light: the chromatograms show principal spots at about the same RF value; and the sum of the intensities of any secondary spots, if present in the chromatogram from the Test preparation, is not greater than 1% of that of the principal spot from Solution A. [NOTE—The relative intensities of the principal spots from the Standard preparations are: Solution A, 1; Solution B, 0.01; Solution C, 0.005; and Solution D, 0.0025.]
Organic volatile impurities, Method V 467: meets the requirements.
Solvent— Use dimethyl sulfoxide.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 180 mg of Butalbital, accurately weighed, in a mixture of 25 mL of alcohol and 25 mL of sodium carbonate solution (3 in 100), and titrate with 0.1 N silver nitrate VS, determining the endpoint electrometrically, using a silver electrode, either with a suitable reference electrode containing a saturated aqueous solution of potassium nitrate, or a combination electrode in which the reference portion of the electrode contains a saturated aqueous solution of potassium nitrate. Each mL of 0.1 N silver nitrate is equivalent to 22.43 mg of C11H16N2O3.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 329
Phone Number : 1-301-816-8330