Doxepin Hydrochloride Oral Solution

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

Doxepin Hydrochloride Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of doxepin (C19H21NO).

2 IDENTIFICATION

A.

Mobile phase: Add 0.2 mL of diethylamine to a solution containing 250 ml. of chloroform and 750 ml of acetonitrile in a vacuum flask. Before use, degas the contents of the flask by stirring vigorously with a magnetic stirrer, while applying vacuum, for 10 min.

Standard solution: 0.44 mg/mL of USP Doxepin Hydrochloride RS in Mobile phase

Sample solution: To 5.0 mL of the Oral Solution in a 60-ml separator add 1 mL of sodium hydroxide solution (1 in 25), 1 g of sodium chloride, and 5.0 mL of ethyl acetate. Shake the mixture vigorously for 1 min. Allow the phases to separate, transfer 1.0 mL of the clear upper phase to a 25-ml volumetric flask, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 254 nm

Column: 2-mm x 50-cm; packed with silica microspheres

Flow rate: 0.4 mL/min

Injection volume: 4 µl.

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The chromatogram of the Sample solution exhibits two peaks having retention times that are identical with those obtained with the Standard solution,

3 ASSAY

PROCEDURE

Diluent: Dilute hydrochloric acid (1 in 120)

Standard stock solution: 1.1 mg/mL of USP Doxepin Hydrochloride RS (1.0 mg/mL of doxepin) in Diluent

Standard solution: Dilute 4.0 mL. of Standard stock solution to 50 mL using Diluent. Transfer 15.0 mL of the resulting solution to a 125-mL separator, and extract with two 20-ml. portions of ether. Dilute 10.0 ml. of the extracted aqueous phase to 25.0 mL using Diluent.

Sample stock solution: Nominally 1 mg/ml. of doxepin from Oral Solution in Diluent

Sample solution: Dilute 4.0 of Sample stock solution to 50 mL using Diluent. Transfer 15.0 mL of the resulting solution to a 125-ml separator, and extract with two 20-ml. portions of ether. Dilute 10.0 mL of the extracted aqueous phase to 25.0 ml. using Diluent.

Instrumental conditions

Mode: UV

Analytical wavelength: Maximum absorbance at about 292 nm

Cell: 1 cm

Blank: Diluent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxepin (C, H, NO) in the Oral Solution taken:

Result = (A_u/A_s) x (C_s/C_u) × (M_r1/M_r2) ×100

A_u = absorbance of the Sample solution

A_s = absorbance of the Standard solution

C_s = concentration of USP Doxepin Hydrochloride RS in the Standard solution (mg/mL)

C_u = nominal concentration of doxepin in the Sample solution (mg/mL)

M_r1 = molecular weight of doxepin, 279.38

M_r2= olecular weight of doxepin hydrochloride, 315.84

Acceptance criteria: 90.0%-110%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905): Meets the requirements for Oral Solution packaged in single-unit containers

DELIVERABLE VOLUME (698): Meets the requirements for Oral Solution packaged in multiple-unit containers

5 SPECIFIC TESTS

PH (791)

Analysis: Allow the portion of Oral Solution under test to remain in contact with the electrodes for 15 min before the measurement.

Acceptance criteria: 4.0-7.0

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers.

LABELING: Label the Oral Solution to indicate that each dose is to be diluted with water or other suitable fluid to approximately 120 mL just before administration.