Cimetidine

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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C₁₀H₁₆N₆S    252.34 

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

2-Cyano-1-methyl-3-[2-[[(5-methylimidazol-4-yl)methyl]thio]ethyl]guanidine CAS RN®: 51481-61-9; UNII: 80061L1WGD. 

1 DEFINITION 

Cimetidine contains NLT 98.0% and NMT 102.0% of cimetidine (C₁₀H₁₆N₆S), calculated on the dried basis.  

2 IDENTIFICATION

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

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B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1- Aug-2022) 

3 ASSAY 

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Procedure 

Mobile phase: Methanol, water, and phosphoric acid (20: 80: 0.03) 

Standard stock solution: 0.4 mg/mL of USP Cimetidine RS prepared as follows. Accurately weigh and transfer an appropriate amount of USP Cimetidine RS in a suitable flask. Add 20% of the nal volume of methanol to dissolve, and dilute with water to volume. Standard solution: 0.01 mg/mL of USP Cimetidine RS in Mobile phase from the Standard stock solution 

Sample stock solution: 0.4 mg/mL of Cimetidine prepared as follows. Accurately weigh and transfer an appropriate amount of Cimetidine in a suitable flask. Add 20% of the nal volume of methanol to dissolve, and dilute with water to volume. 

Sample solution: 0.01 mg/mL of Cimetidine in Mobile phase from the Sample stock solution 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm. For Identification B, use a diode array detector in the range of 190–400 nm.  Column: 3.9-mm × 30-cm; packing L1 

Flow rate: 2.0 mL/min 

Injection volume: 50 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0  

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of cimetidine (C₁₀H₁₆N₆S) in the portion of Cimetidine taken: 

Result = (r_U/r_S) × (C_S/C_U)  × 100 

r_U = peak response of cimetidine  from the Sample solution 

r_S = peak response of cimetidine  from the Standard solution 

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

C_U = nominal concentration of cimetidine 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% 

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Organic Impurities 

Mobile phase: Mix 240 mL of methanol, 0.3 mL of phosphoric acid, 940 mg of sodium 1-hexanesulfonate, and sufficient water to make 1 L, and filter. 

Standard solution: 0.80 µg/mL of USP Cimetidine RS in Mobile phase 

Sample solution: 0.4 mg/mL of Cimetidine in Mobile phase. Sonicate for NLT 15 min to dissolve.  Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 4.6-mm × 25-cm; packing L1 

Flow rate: 2.0 mL/min 

Injection volume: 50 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0  

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each impurity in the portion of Cimetidine 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 cimetidine from the Standard solution

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

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

Acceptance criteria: See Table 1. 

Table 1 

5 SPECIFIC TESTS 

Delete the following: 

Melting Range or Temperature 〈741〉: 139°–144°  

Loss on Drying 〈731〉 

Analysis: Dry a sample at 110° for 2 h. 

Acceptance criteria: NMT 1.0% 

6 ADDITIONAL REQUIREMENTS 

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

USP Reference Standards 〈11〉 

USP Cimetidine RS