Cyclizine Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
DOWNLOAD PDF HERE

1 DEFINITION

Cyclizine Hydrochloride contains NLT 98.0% and NMT 100.5% of cyclizine hydrochloride (C₁₈H₂₂N₂ . HCI), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

2.1 A. ASPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

2.2 B. IDENTIFICATION TESTS-GENERAL, Chloride (191):

Meets the requirements

3 ASSAY

3.1 PROCEDURE

[NOTE-In order to avoid overheating in the reaction medium, mix thoroughly throughout and stop the titration immediately after the endpoint has been reached.]

Sample: 120 mg.

Analysis: Dissolve the Sample in 15 mL of anhydrous formic acid. Add 40 mL of acetic anhydride, and titrate with 0.1 N perchloric acid VS.

Perform a blank determination (see Titrimetry (541)), and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 15.14 mg of cyclizine hydrochloride (C18H22N2 HCI).

Acceptance criteria: 98.0%-100.5% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.2%

4.2 ORGANIC IMPURITIES

[NOTE-Prepare solutions immediately before use.]

Standard solution: 0.05 mg/mL of USP Cyclizine Hydrochloride RS in methanol

Impurity standard solution: 0.25 mg/mL each of USP Cyclizine Hydrochloride RS, USP Cyclizine Related Compound A RS, and USP Benzhydrol RS in methanol

Sample solution: Prepare a solution containing 50 mg/mL of Cyclizine Hydrochloride by dissolving a suitable amount first in methanol, using 80% of the final volume, and then diluting with 1 N sodium hydroxide to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.33 - mm * 25 - m coated with a 0.5-µm film of phase G27

Temperatures

Injection port: 250°

Detector: 290°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 1 mL/min

Injection volume: 1 µL

Injection type: Split ratio, 1:25

System suitability

Sample: Impurity standard solution

Suitability requirements

Peak-to-valley ratio: NLT 50 between cyclizine related compound A and methanol

Analysis

Samples: Standard solution, Impurity standard solution, and Sample solution

Calculate the percentage of cyclizine related compound A and benzhydrol in the portion of Cyclizine Hydrochloride taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each related compound from the Sample solution

r_s = peak response of the corresponding related compound from the Impurity standard solution

C_s = concentration of the corresponding related compound in the Impurity standard solution (mg/mL)

C_u = concentration of Cyclizine Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Cyclizine Hydrochloride taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of cyclizine from the Standard solution

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

C_u = concentration of Cyclizine Hydrochloride in the Sample solution (mg/mL)

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

Table 2

5 SPECIFIC TESTS

5.1 PH (791).

Sample solution: 20 mg/mL in a mixture of alcohol and water (2:3)

Acceptance criteria: 4.5-5.5

5.2 LOSS ON DRYING (731).

Analysis: Dry a sample at 120° for 3 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

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

6.2 USP REFERENCE STANDARDS (11)

USP Cyclizine Hydrochloride RS

USP Cyclizine Related Compound A RS

1-Methylpiperazine.

C₅H₁₂N₂      100.16

USP Benzhydrol RS

Diphenylmethanol.

C₁₃H₁₂O       184.23