Hydroxyzine Hydrochloride Injection

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 Injection is a sterile solution of Hydroxyzine Hydrochloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ . 2HCl).

2 IDENTIFICATION

A.

Standard solution: 20 µg/mL of USP Hydroxyzine Hydrochloride RS in 0.1 N hydrochloric acid

Sample solution: Nominally 20 µg/mL of hydroxyzine hydrochloride from Injection in 0.1 N hydrochloric acid

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as that of the Standard solution, concomitantly measured.

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

3 ASSAY

3.1 PROCEDURE

Protect the Standard solution and Sample solution from light.

Buffer: 2 g/L of dibasic potassium phosphate and 8 g/L of monobasic potassium phosphate adjusted with 10 N potassium hydroxide to a pH of 6.6

Mobile phase: Methanol and Buffer (65:35)

Standard solution: 0.25 mg/mL of USP Hydroxyzine Hydrochloride RS and 0.5 µg/mL of USP 4-Chlorobenzophenone RS in Mobile phase

Sample solution: Nominally 0.25 mg/mL of hydroxyzine hydrochloride from Injection in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4-mm x 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for 4-chlorobenzophenone and hydroxyzine are 0.75 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between the 4-chlorobenzophenone and hydroxyzine peaks

Tailing factor: NMT 2.5 for the 4-chlorobenzophenone and hydroxyzine peaks

Relative standard deviation: NMT 2.0% for the hydroxyzine peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of hydroxyzine hydrochloride (C₂₁H₂₇ClN₂O₂ . 2HCl) in the portion of Injection 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 s

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 IMPURITIES

4.1 LIMIT OF 4-CHLOROBENZOPHENONE

Mobile phase, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 4-chlorobenzophenone in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

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

r_S = peak response of 4-chlorobenzophenone in the Standard solution s

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

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

Acceptance criteria: NMT 0.2%

5 SPECIFIC TESTS

PH (791): 3.5-6.0

BACTERIAL ENDOTOXINS TEST (85): NMT 3.6 USP Endotoxin Units/mg of hydroxyzine hydrochloride

OTHER REQUIREMENTS: Meets the requirements in Injections and Implanted Drug Products (1)

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-dose or multiple-dose containers, protected from light. Store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP 4-Chlorobenzophenone RS  C₁₃H₉ClO  216.66

USP Hydroxyzine Hydrochloride RS