Cimetidine Hydrochloride

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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C₁₀H₁₆N₆S₆ HCI 288.80

Guanidine, N"-cyano-N-methyl-N-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]-, monohydrochloride;

2-Cyano-1-methyl-3-[2-[[(5-methylimidazol-4-yl)methyl]thio]ethyl]guanidine monohydrochloride CAS RN: 70059-30-2; UNII: WF10491673.

1 DEFINITION

Cimetidine Hydrochloride contains NLT 98.0% and NMT 102.0% of cimetidine hydrochloride (C₁₀H₁₆N₆S₆), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Change to read:

B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 197U (CN 1-MAY-2020)

Sample solution: 14 µg/mL

Medium: 0.1 N sulfuric acid

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Mobile phase: Transfer 200 mL of methanol and 0.3 mL of phosphoric acid to a 1000-mL volumetric flask, dilute with water to volume, and filter.

Standard stock solution: 0.5 mg/mL of USP Cimetidine Hydrochloride RS in a mixture of methanol and water (1:4)

Standard solution: 12.5 µg/mL of USP Cimetidine Hydrochloride RS in Mobile phase from Standard stock solution

Sample stock solution: 0.5 mg/mL of Cimetidine Hydrochloride in a mixture of methanol and water, prepared by initially dissolving the sample in water using 20% of the final volume, adding methanol using 20% of the final volume, and diluting that solution with water to volume

Sample solution: 12.5 µg/mL of Cimetidine Hydrochloride in Mobile phase from Sample stock solution

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm x 30-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 50 µL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Capacity factor, k': NLT 0.6

Column efficiency: NLT 1000 theoretical plates

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of cimetidine hydrochloride (C₁₀H₁₆N₆S₆.HCI) in the portion of Cimetidine Hydrochloride taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Cimetidine Hydrochloride in the Standard solution (mg/ml.)

C_U = concentration of Cimetidine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.2%

5 ORGANIC IMPURITIES

Mobile phase: Transfer 940 mg of sodium 1-hexanesulfonate to a 1000-mL volumetric flask, add 240 mL of methanol followed by 0.3 mL of phosphoric acid, and dilute with water to volume. Filter before use.

Sample solution: 0.4 mg/mL of Cimetidine Hydrochloride in Mobile phase

Diluted sample solution: 0.8 µg/mL of Cimetidine Hydrochloride in Mobile phase from the the Sample solution

System suitability solution: Dissolve 50 mg of Cimetidine Hydrochloride in 10 mL of 1 N hydrochloric acid, heat on a steam bath for about 10 min (or boil on a hot plate for about 2 min), and allow to cool. Dilute a suitable volume of this solution with Mobile phase to obtain a solution containing 2 µg/mL.. Use this solution within 24 h of its preparation. Adjusment of the heating step may be necessary to achieve a satisfactory amide analog peak response for the measurement of the resolution between the cimetidine and the amide analog peaks.

Chromatographic system

(See Chromatography (621). System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm x 25-cm; packing L1

Flow rate: 2 mL/min

Injection volume: 50 µL

System suitability

Samples: System suitability solution and Diluted sample solution

Suitability requirements

Resolution: NLT 4.0 between the cimetidine and the amide analog peaks, System suitability solution

Capacity factor, k': NLT 3.0 , Diluted sample solution

Column efficiency: NLT 2000 theoretical plates, Diluted sample solution

Relative standard deviation: NMT 7.0%, Diluted sample solution

Analysis

Samples: Sample solution and Diluted sample solution

Calculate the percentage of each impurity in the portion of Cimetidine Hydrochloride taken:

Result = (r_U/r_S) x D x 100

r_U = peak response for each impurity from the Sample solution

r_S  = peak response of cimetidine from the Diluted sample solution

D = dilution factor to prepare the Diluted sample solution from the Sample solution, 0.002

Acceptance criteria

Any individual impurity: NMT 0.2%

Total impurities: NMT 1.0%

6 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry a sample at 105° for 2 h.

Acceptance criteria: NMT 0.5%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

USP Reference Standards 〈11〉

USP Cimetidine Hydrochloride RS