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Doxylamine Succinate
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C17H22N2O·C4H6O4 388.46

Ethanamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]-, butanedioate (1:1).
2-[-[2-(Dimethylamino)ethoxy]--methylbenzyl]pyridine succinate (1:1) [562-10-7].
» Doxylamine Succinate contains not less than 98.0 percent and not more than 101.0 percent of C17H22N2O·C4H6O4, calculated on the dried basis.
Packaging and storage— Preserve in well-closed, light-resistant containers.
Identification—
A: Ultraviolet absorption 197U—
Solution: 20 µg per mL.
Medium: 0.1 N hydrochloric acid.
Absorptivities at 262 nm, calculated on the dried basis, do not differ by more 3.0%.
B: It meets the requirements under Identification—Organic Nitrogenous Bases 181.
C: Dissolve about 500 mg in 5 mL of water, and add a slight excess of 6 N ammonium hydroxide. Extract the liberated doxylamine with several portions of ether, discard the ether extracts, and evaporate the aqueous solution on a steam bath to dryness. Add 2 mL of 3 N hydrochloric acid, and again evaporate on the steam bath to dryness. Cool, add about 10 mL of ether, allow to stand for a few minutes, and decant the clear supernatant. Evaporate the ether solution to dryness, and dry the residue at 105 for 30 minutes: the succinic acid so obtained melts between 184 and 188, the procedure for Class I being used (see Melting Range or Temperature 741).
Melting range, Class I 741: between 103 and 108, but the range between beginning and end of melting does not exceed 3.
Loss on drying 731— Dry it in vacuum over phosphorus pentoxide for 5 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Volatile related compounds— Dissolve 650 mg in 20 mL of 0.1 N hydrochloric acid in a separator. Render the solution alkaline with 2.5 N sodium hydroxide, and immediately extract with four 25-mL portions of ether, filtering each extract through an ether-saturated pledget of cotton. Evaporate the combined ether extracts on a water bath with the aid of a current of air to dryness at a temperature not exceeding 50, and dissolve the residue in 5 mL of alcohol. Inject about 1 µL of this solution into a suitable gas chromatograph (see Chromatography 621) equipped with a flame-ionization detector. Under typical conditions, the instrument contains a 2-m × 4-mm glass column containing 5% packing G16 and 5% packing G12 on 60- to 80-mesh S1A. The column is maintained at about 212, the injection port and detector block are maintained at about 250, and dry helium is used as the carrier gas. The total relative area of all extraneous peaks (except that of the solvent peak) does not exceed 2.0%, and the relative area of any individual extraneous peak does not exceed 1.0%.
Organic volatile impurities, Method I 467: meets the requirements.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 500 mg of Doxylamine Succinate, accurately weighed, in 80 mL of glacial acetic acid. Add crystal violet TS, and titrate with 0.1 N perchloric acid VS to an emerald-green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 19.42 mg of C17H22N2O·C4H6O4.
Auxiliary Information— Staff Liaison : Daniel K. Bempong, Ph.D., Scientist
Expert Committee : (MDPS05) Monograph Development-Pulmonary and Steroids
USP29–NF24 Page 767
Phone Number : 1-301-816-8143