Hydroxyzine Pamoate

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

Hydroxyzine Pamoate contains NLT 97.0% and NMT 102.0% of hydroxyzine pamoate (C₂₁H₂₇ClN₂O₂ · C₂₃H₁₆O₆), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy:

[Note—Methods described in 〈197K〉 or 〈197A〉 may be used.]

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

3 ASSAY

Procedure

Solution A: To each L of water, add 1.0 mL of stronger ammonia water.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Diluent: Acetonitrile and Solution A (80:20)

System suitability solution: 1 µg/mL of USP Hydroxyzine Pamoate RS, 3 µg/mL of USP Hydroxyzine Related Compound A RS, and 1 µg/mL of USP 4-Chlorobenzophenone RS in Diluent

Standard solution: 0.1 mg/mL of USP Hydroxyzine Pamoate RS in Diluent

Sample solution: 0.1 mg/mL of Hydroxyzine Pamoate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L1

[Note—Rinse the column with a solution of acetonitrile and water (20:80) and then with a solution of acetonitrile and water (80:20) after each analysis.]

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention time for 4-chlorobenzophenone is 1.1. See Table 2 for the relative retention times for other compounds.]

Suitability requirements

Resolution: NLT 1.5 between hydroxyzine and hydroxyzine related compound A;

NLT 1.5 between hydroxyzine related compound A and 4-chlorobenzophenone, System suitability solution

Tailing factor: NMT 1.5 for hydroxyzine, Standard solution

Relative standard deviation: NMT 0.73% for hydroxyzine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hydroxyzine pamoate (C₂₁H₂₇ClN₂O₂ · C₂₃H₁₆O₆) in the portion of Hydroxyzine Pamoate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of hydroxyzine from the Sample solution

rₛ = peak response of hydroxyzine from the Standard solution

Cₛ = concentration of USP Hydroxyzine Pamoate RS in the Standard solution (mg/mL)

Cᵤ = concentration of Hydroxyzine Pamoate in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Change to read:

Organic Impurities

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

Standard solution: 1 µg/mL of USP Hydroxyzine Pamoate RS, 3 µg/mL of USP Hydroxyzine Related Compound A RS, and 1 µg/mL of USP 4-Chlorobenzophenone RS in Diluent

Sample solution: 1000 µg/mL of Hydroxyzine Pamoate in Diluent

System suitability

Sample: Standard solution

[Note—The relative retention time for 4-chlorobenzophenone is 1.1. See Table 2 for the relative retention times for other compounds.]

Suitability requirements

Resolution: NLT 1.5 between hydroxyzine and hydroxyzine related compound A;

NLT 1.5 between hydroxyzine related compound A and ▲4-chlorobenzophenone▲ (ERR 1-Jun-2021)

Relative standard deviation: NMT 5.0% each for hydroxyzine and hydroxyzine related compound A

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of hydroxyzine related compound A in the portion of Hydroxyzine Pamoate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of hydroxyzine related compound A from the Sample solution

rₛ = peak response of hydroxyzine related compound A from the Standard solution

Cₛ = concentration of USP Hydroxyzine Related Compound A RS in the Standard solution (µg/mL)

Cᵤ = concentration of Hydroxyzine Pamoate in the Sample solution (µg/mL)

Calculate the percentage of decloxizine and each unspecified impurity in the portion of Hydroxyzine Pamoate taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response of decloxizine or each unspecified impurity from the Sample solution

rₛ = peak response of hydroxyzine from the Standard solution

Cₛ = concentration of USP Hydroxyzine Pamoate RS in the Standard solution (µg/mL)

Cᵤ = concentration of Hydroxyzine Pamoate in the Sample solution (µg/mL)

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

Table 2

ᵃ This peak is due to the pamoate counterion; hence it is not an impurity and should not be included in the total impurities.

ᵇ 2-[2-(4-Benzhydrylpiperazin-1-yl)ethoxy]ethanol.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 5.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store below 30°.

USP Reference Standards 〈11〉

USP 4-Chlorobenzophenone RS

4-Chlorobenzophenone.

C₁₃H₉ClO 216.66

USP Hydroxyzine Related Compound A RS

1-[(4-Chlorophenyl)phenylmethyl]piperazine.

C₁₇H₁₉ClN₂ 286.80

USP Hydroxyzine Pamoate RS