C
17H
21NO·C
7H
7ClN
4O
2
469.96
1
H-Purine-2,6-dione, 8-chloro-3,7-dihydro-1,3-dimethyl-, compd. with 2-(diphenylmethoxy)-
N,
N-dimethylethanamine (1:1).
8-Chlorotheophylline, compound with 2-(diphenylmethoxy)-
N,
N-dimethylethylamine (1:1)
[
523-87-5].
Packaging and storage—
Preserve in well-closed containers.
Identification—
B:
Dissolve about 250 mg in 15 mL of diluted alcohol, add 15 mL of water and 2 mL of 2 N sulfuric acid, and cool for 30 minutes. Scratch the inside of the container to facilitate crystallization. Filter the mixture, wash the crystals with a few mL of ice-cold water, and dry the crystals: the 8-chlorotheophylline melts between 300
and 305
with decomposition.
C:
To about 10 mg of the 8-chlorotheophylline obtained in
Identification test
B, contained in a porcelain dish, add 1 mL of hydrochloric acid and 100 mg of potassium chlorate, evaporate on a steam bath to dryness, and invert the dish over a vessel containing a few drops of
ammonia TS: the residue acquires a purple color, which is destroyed by solutions of fixed alkalies.
D:
Mix about 50 mg of the 8-chlorotheophylline obtained in
Identification test
B with about 500 mg of sodium peroxide in a nickel crucible, and heat until the mass is well sintered. Dissolve the melt in 20 mL of water, acidify with 2 N nitric acid, filter if necessary, and add 1 mL of
silver nitrate TS: a curdy, white precipitate is formed, and it is soluble in 6 N ammonium hydroxide and reappears upon acidification with nitric acid.
Loss on drying 
731
—
Dry it in vacuum over phosphorus pentoxide for 24 hours: it loses not more than 0.5% of its weight.
Bromide and iodide—
Mix in a test tube 100 mg of Dimenhydrinate, 50 mg of sodium nitrite, and 10 mL of chloroform. Add 10 mL of 3 N hydrochloric acid, insert the stopper in the tube, and shake: the chloroform remains colorless.
Chloride—
When the ammoniacal filtrate from the precipitation of silver chlorotheophylline in the
Assay for 8-chlorotheophylline is acidified preparatory to titration, the solution shows not more than a faint opalescence.
Organic volatile impurities, Method V 467:
meets the requirements.
Solvent—
Use dimethyl sulfoxide.
Assay for diphenhydramine—
Dissolve about 150 mg of Dimenhydrinate, accurately weighed, in 75 mL of glacial acetic acid, and titrate with 0.05 N perchloric acid VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.05 N perchloric acid is equivalent to 12.77 mg of diphenhydramine (C17H21NO).
Assay for 8-chlorotheophylline—
Place about 800 mg of Dimenhydrinate, accurately weighed, in a 200-mL volumetric flask, add 50 mL of water, 3 mL of 6 N ammonium hydroxide, and 6 mL of ammonium nitrate solution (1 in 10), and warm the mixture on a steam bath for 5 minutes. Add 25.0 mL of 0.1 N silver nitrate VS, mix, and warm on a steam bath for 15 minutes with frequent shaking. Cool, dilute with water to volume, mix, and allow the precipitate to settle. Filter through a dry filter paper, discarding the first 20 mL of the filtrate. Pipet 100 mL of the filtrate into a 250-mL flask, acidify with nitric acid, and add an excess of 3 mL of the acid. Add 2 mL of
ferric ammonium sulfate TS, and titrate the excess silver nitrate with 0.1 N ammonium thiocyanate VS. Each mL of 0.1 N silver nitrate is equivalent to 21.46 mg of C
7H
7ClN
4O
2.
Auxiliary Information—
Staff Liaison :
Elena Gonikberg, Ph.D., Scientist
Expert Committee : (MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine
USP29–NF24 Page 720
Pharmacopeial Forum : Volume No. 29(5) Page 1466
Phone Number : 1-301-816-8251
;)