Doxylamine Succinate Tablets

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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1 DEFINITION

Doxylamine Succinate Tablets contain NLT 92.0% and NMT 108.0% of the labeled amount of doxylamine succinate (C₁₇H₂₂N₂O · C₄H₆O₄)

2 IDENTIFICATION

Delete the following:

A. Tablets meet the requirements under Identification-Organic Nitrogenous Base (181)

Add the following:

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay

Add the following:

B. The UV-Vis absorption spectra of the major peak of the Sample solution exhibit maxima and minima at the same wavelengths as those of the corresponding peak of the Standard solution, as obtained in the Assay 

3 ASSAY

Change to read:

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 Solution 8 (90:10)

Standard solution: 0.1 mg/ml. of USP Doxylamine Succinate RS in Diluent

Sample solution: Nominally 0.1 mg/ml of doxylamine succinate in Diluent prepared as follows. Transfer an appropriate quantity of doxylamine succinate from NLT 10 finely powdered Tablets to a suitable volumetric flask and dilute with Diluent to volume. (NOTE-Sonication or shaking may be necessary. Centrifuge or pass a portion of this solution through a suitable filter.]

Chromatographic system

(See Chromatography (621), System Surtability)

Mode: LC

Detector: UV 262 nm. For Identification B, use a diode array detector in the range of 230-400 nm.

Column: 4.6-mm x 15-cm; 5-um packing LZ

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

USP-NF Doxylamine Succinate Tablets

2/17/25, 11:04 PM

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxylamine succinate (C₁₇H₂₂N₂O · C₄H₆O₄) in the portion of Tablets 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: 92.0%-108.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Medium: 0.01. N hydrochloric acid: 900 ml

Apparatus 2: 50 rpm

Time: 30 min

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857 ).)

Mode: UV

Analytical wavelength: 262 nm

Standard solution: LISP Doxylamine Succinate RS in Medium

Sample solution: Sample per Dissolution (711). Dilute with Medium to a concentration that is similar to the Standard solution.

Analysis

Samples: Standard solution and Sample solution

Determine the percentage of the labeled amount of doxylamine succinate (C₁₇H₂₂N₂O · C₄H₆O₄) dissolved

Tolerances: NLT 80% (0) of the labeled amount of doxylamine succinate (C₁₇H₂₂N₂O · C₄H₆O₄) is dissolved.

Change to read:

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

Add the following:

ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.001 mg/mL each of USP Doxylamine Succinate RS and USP Carbinoxamine Related Compound C. RS in Diluent

Standard solution: 0.001 mg/ml of USP Doxylamine Succinate RS in Diluent

Sample solution: Nominally 1.0 mg/ml of doxylamine succinate in Diluent prepared as follows. Finely powder NLT 10 Tablets and transfer a portion of the powder to an appropriate volumetric flask. Dilute with Diluent to volume [NOTE-Sonication or shaking may be necessary Centrifuge or pass a portion of this solution through a suitable filter]

System suitability

Samples: System suitability solution and Standard solution [NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 2.0 between doxylamine and carbinoxamine related compound C. System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified and unspecified degradation product in the portion of Tablets taken:

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

r_U = peak response of each specified and unspecified degradation product 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)

F = relative response factor of each specied and any unspecied degradation product (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak below 0.05%Acceptance criteria: See Table 2. Disregard any peak below 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.

6 ADDITIONAL REQUIREMENTS

Change to read:

PACKAGING AND STORAGE: Store at controlled room temperature in tight light-resistant containers.