Hydroxyzine 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

Hydroxyzine Hydrochloride Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ . 2HCl).

2 IDENTIFICATION

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

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: Trifluoroacetic acid and water (0.1:99.9)

Solution B: Trifluoroacetic acid and acetonitrile (0.05:99.95)

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (30:70)

Standard solution: 0.05 mg/mL of USP Hydroxyzine Hydrochloride RS in Diluent

Sample stock solution: Nominally 0.5 mg/mL of hydroxyzine hydrochloride from Oral Solution in Diluent prepared as follows. Transfer a portion of Oral Solution, equivalent to 25 mg of hydroxyzine hydrochloride, to a 50-mL volumetric flask. Dissolve and dilute with Diluent to volume.

Sample solution: Nominally 0.05 mg/mL of hydroxyzine hydrochloride from the Sample stock solution in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 2.1-mm × 15-cm; 1.8-µm packing L1

Column temperature: 30°

Flow rate: 0.3 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ . 2HCl) in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of hydroxyzine from the Sample solution

r_S = peak response of hydroxyzine from the Standard solution

C_S = concentration of USP Hydroxyzine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of hydroxyzine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

UNIFORMITY OF DOSAGE UNITS (905)

For single-unit containers

Acceptance criteria: Meets the requirements

DELIVERABLE VOLUME (698)

For multiple-unit containers

Acceptance criteria: Meets the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, and Diluent: Prepare as directed in the Assay.

Standard stock solution: 25.0 µg/mL each of USP Hydroxyzine Hydrochloride RS, USP Hydroxyzine Related Compound A RS, and USP 4-Chlorobenzophenone RS in Diluent

Standard solution: 1.0 µg/mL each of USP Hydroxyzine Hydrochloride RS, USP Hydroxyzine Related Compound A RS, and USP 4-Chlorobenzophenone RS from the Standard stock solution in Diluent

Sample solution: Nominally 500 µg/mL of hydroxyzine hydrochloride from Oral Solution in Diluent prepared as follows. Transfer a portion of Oral Solution, equivalent to 25 mg of hydroxyzine hydrochloride, to a 50-mL volumetric flask. Dissolve and dilute with Diluent to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detectors

Hydroxyzine related compound A and hydroxyzine hydrochloride: UV 230 nm

4-Chlorobenzophenone: UV 254 nm

Column: 2.1-mm × 15-cm; 1.8-µm packing L1

Column temperature: 30°

Flow rate: 0.3 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

[Note-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 5.0 between hydroxyzine related compound A and hydroxyzine

Relative standard deviation: NMT 3.0% for hydroxyzine related compound A, hydroxyzine, and 4-chlorobenzophenone

Analysis

Samples: Standard solution and Sample solution

For impurities detected at UV 230 nm

Calculate the percentage of any individual unspecified degradation product in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any individual unspecified degradation product from the Sample solution

r_S = peak response of hydroxyzine from the Standard solution

C_S = concentration of USP Hydroxyzine Hydrochloride RS in the Standard solution (µg/mL)

C_U = nominal concentration of hydroxyzine hydrochloride in the Sample solution (µg/mL)

For 4-chlorobenzophenone detected at UV 254 nm

Calculate the percentage of 4-chlorobenzophenone in the portion of Oral Solution taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of 4-chlorobenzophenone from the Sample solution

r_S = peak response of 4-chlorobenzophenone from the Standard solution

C_S = concentration of USP 4-Chlorobenzophenone RS in the Standard solution (µg/mL)

C_U = nominal concentration of hydroxyzine hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. Disregard any peak below 0.03%.

Table 2

^a This is a process impurity that is controlled in the drug substance. It is not to be reported or included in the total degradation products.

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS (11)

USP 4-Chlorobenzophenone RS

4-Chlorobenzophenone

C₁₃H₉ClO  216.66

USP Hydroxyzine Hydrochloride RS

USP Hydroxyzine Related Compound A RS

p-Chlorobenzhydrylpiperazine;

Also known as 1-[(4-Chlorophenyl)phenylmethyl]piperazine

C₁₇H₁₉ClN₂  286.80