Cimetidine in Sodium Chloride 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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Cimetidine in Sodium Chloride Injection is a sterile solution of Cimetidine Hydrochloride and Sodium Chloride in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amount of cimetidine (C₁₀H₁₆N₆S) and NLT 95.0% and NMT 110.0% of the labeled amount of sodium chloride (NaCl). 

1 IDENTIFICATION 

A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. B. Identification Tests—General, Sodium〈191〉andChloride〈191〉: Meets the requirements 

2 ASSAY 

Cimetidine 

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 solution: Nominally 10.0 µg/mL of cimetidine, prepared as follows. Transfer an accurately measured volume of Injection, equivalent to about 2 mg of cimetidine, to a 200-mL volumetric flask, and dilute with Mobile phase to volume. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 220 nm 

Column: 3.9-mm × 30-cm; packing L1 

Flow rate: 2 mL/min 

Injection volume: 50 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Capacity factor, k′: NLT 0.6 

Column efficiency: NLT 1000 theoretical plates 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of cimetidine (C₁₀H₁₆N₆S) in the portion of Injection taken: 

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

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

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

M_r1 = molecular weight of cimetidine, 252.34 

M_r2 = molecular weight of cimetidine hydrochloride, 288.81 

Acceptance criteria: 90.0%–110.0% 

Sodium Chloride 

Sample solution: Dilute a volume of Injection with water to obtain a solution containing 0.5 mg/mL of sodium chloride. Analysis: Determine the total amount of chloride, A, in the Sample solution, in mg, by titrating the Sample solution with 0.1 N silver nitrate VS, using a silver–silver chloride electrode. Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of chloride. 

To correct for the chloride present as cimetidine hydrochloride, calculate the concentration of chloride, C, due to sodium chloride, in mg/mL, in the Sample solution: 

Result = (A/V) − [W × (M_Cl /M_r1)] 

A = total amount of chloride in the Sample solution (mg) 

V = volume of the Injection taken to prepare the Sample solution (mL) 

W = quantity of cimetidine in the Injection, as determined in the Assay for Cimetidine (mg/mL) 

M_Cl = atomic weight of chloride, 35.453 

M_r1 = molecular weight of cimetidine, 252.34 

Calculate the percentage of the labeled amount of sodium chloride (NaCl) in the portion of Injection taken: 

Result = (C/C_U) × (M_NaCl/M_Cl) × 100 

C = concentration of chloride due to sodium chloride in the Sample solution (mg/mL) 

C = nominal concentration of sodium chloride in the Sample solution (mg/mL) 

M_NaCl = molecular weight of sodium chloride, 58.443 

M_Cl = atomic weight of chloride, 35.453 

Acceptance criteria: 95.0%–110.0% 

3 SPECIFIC TESTS 

Bacterial Endotoxins Test 〈85〉: NMT 0.5 USP Endotoxin Unit/mg of cimetidine hydrochloride 

pH 〈791〉: 5.0–7.0 

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉. 

4 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in single-dose glass or plastic containers. Glass containers are preferably of Type I or Type II glass. USP Reference Standards 〈11〉 

USP Cimetidine Hydrochloride RS