Doxylamine Succinate

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Ethanamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy]-, butanedioate (1:1);

2-[α-[2-(Dimethylamino)ethoxy]-α-methylbenzyl]pyridine succinate (1:1);

N,N-Dimethyl-2-[1-phenyl-1-(pyridin-2-yl)ethoxy]ethan-1-amine succinate CAS RN^®: 562-10-7.

1 DEFINITION

Change to read:

Doxylamine Succinate contains NLT 98.0% and NMT 102.0% (USP 1-May-2019) of doxylamine succinate (C₁₇H₂₂N₂O · C₄H₆O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

ASPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy 1970 (CN 1--2020)

Analytical wavelength: 262 nm

Sample solution: 20 µg/mL of Doxylamine Succinate in 0.1 N hydrochloric acid

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%

Delete the following:

B. IDENTIFICATION ORGANIC NITROGENOUS BASES (181): It meets the requirements (USP 1-May-2019)

Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-May-2019)

C.

Sample solution: Dissolve 500 mg of Doxylamine Succinate 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 min.

Acceptance criteria: The succinic acid melts between 184" and 188", as indicated for Class I under Melting Range or Temperature (741), Procedures

3 ASSAY

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PROCEDURE

Solution A: 50 mM ammonium acetate in water, adjusted with glacial acetic acid to a pH of 4.0

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Solution A and Solition (9010)

Standard solution: 0.1 mg/ml of USP Dondamine Succinate RS Σλλητ

Sample solution: 0.1 mgnnt of Doxylamine Suconate in Diluent

Chromatographic system

(See Chromatogracity 1021 System Stay)

Mode: LC

Detector: UV 252.nm

Columns: 4.5mx15cm, 8um packing

Column temperature: 30

Flow rate: 1 mL/mem

Injection volume: 20

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2:0

Relative standard deviation: NMT 0,73%

AL

Analysis

Samples: Standards and Sample solution

Calculate the percentage of doxylamine succinate (C₁₇H₂₂N₂O · C₄H₆O₄) inthe portion of Dorylamine Suconate taken:

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response of doxylamine from the Sample solution

r_S = peak response of doxylamine from the Standard solution

C_S = concentration of USP Doxylamine Succinate RS in the Standard solution (mg/mL)

C_U = = nominal concentration of doxylamine succinate in the Sample solution (mg/ml)

Acceptance criteria: 90.05-1020 on the dried basis.

4 IMPURSTIES

Residue on Ignition (281): NMT 0.1%

Delete the following:

VILAFEL RILATED COMPONES

Sample solution: Dissolve 650 mg in 20 ml of 0.1 N hydroctooricand in separator. Rende 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 ale to dryness at a temperature net excserting 50" and dissolve the residue in 5 mL of alcohol.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: DC

Detector: Fissmelonization

Column: 4-mm x 2m glass column containing 5% packing 1210 and 5% pecking 912 on 60- to BUmesh 516

Temperatures

Colume: 212°

Injection port: 250°

Detector block: 250°

Carrier gas: Dry helium

Injection volume: 1μL

Acceptance criteria: NMT 2.00%, the total relative arms of all extraneous peaks (except that of the solvent peak), ane NMT 1.0, the relative area of any individual extraneous peak

Add the following:

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic systent Proceed as directed in the Assay

Standard solution: 0.001 mg/ml each of oxviamine Succinate RS and Carbinoxamine Related Compound CRG in Diuent

Sample solution: 10 mg/ml, of Doxylamine Succinate in Diluent

System suitability

Sample: Standard solution

Nom-See Table 2 for relative retention times

Suitability requirements

Resolution: NUT 2 between doxylammine and carbinoxamine related compound C

Relative standard deviation: NMT 5.0% for the doxylamine and carbinoxamine related compound C peaks

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of carbinoxamine related compound C in the portion of Doxylamine Suconate takerc

Result = (r_U/(r_S) × (C_S /C_U) x 100

r_U = peak response of carbonoxamine related compound C from the Sample solution

r_S = peak response of cartenoxamine related compound C from the Standard solution

C_S = concentration of USP Carbinoxamine Related Compound C RS in the Standard solution (mg/mL)

C_U =  concentration of Doxylamine Succinate in the Sample solution (mg/ml)

Calculate the percentage of each specified and any unspecified impurity in the portion of Doxylamine Succinate taken:

Result = (r_U/(r_S) × (C_S /C_U) x (1/F) x 100

r_U = peak response of each specified and any unspecified impunity from the Sample solution

r_S = peak response of coxylamine from the Standard solution

C_S = concentration of USP Doxylamine Succinate RS in the Standard solution (mg/mL)

C_U = concentration of Doxylamine Succinate in the Sample solution (mg/mL)

F = relative response factor of each specified and any unspecited impurity (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%

^a 2-[1-(2-(Dimethylamino)ethoxy)-1-phenylethyl]pyridine 1-oxide.

^b N,N-Dimethyl-2-(1-(1-oxidopyridin-2-yl)-1-phenylethoxy)ethan-1-amine oxide

^c CN,N-Dimethyl-2-11-phenyl-1-pyridin-4-yl)ethoxyjethan-1-amine

^d Process related impurity. Do not include in calculation of total degradation products.

^e NN-Dimethyl-2-11-phenyl-1-(pyridin-2-yl)ethoxylethan-1-amine oxide

^f 1-Phenyl-1-(pyridin-2-yl)ethan-1-ol.

^g Phenyl (pyridin-2-yl)methanone.

5 SPECIFIC TESTS

Delete the following:

Melting Range or Temperature, Class I (741): 103°–108°, the range between the beginning and end of melting does not exceed 3°.

Loss on Drying (731)

Analysis: Dry under vacuum over phosphorus pentoxide for 5 h.

Acceptance criteria: NMT 0.5%

ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.