Ranitidine Injection

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

To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb ranitidine-inj-20230331. 

1 DEFINITION 

Ranitidine Injection is a sterile solution of Ranitidine Hydrochloride in Water for Injection. It contains the equivalent of NLT 90.0% and NMT 110.0% of the labeled amount of ranitidine (C₁₃H₂₂N₄O₃S).  

2 IDENTIFICATION 

A. The R value of the principal spot of the Sample solution corresponds to that of the Standard solution, as obtained in Organic Impurities. F 

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

ASSAY Procedure 

Buffer: 0.1 M ammonium acetate in water 

Mobile phase: Methanol and Buffer (85:15) 

System suitability solution: 0.112 mg/mL of USP Ranitidine Hydrochloride RS and 0.01 mg/mL of USP Ranitidine Related Compound C RS in Mobile phase 

Standard solution: 0.112 mg/mL of USP Ranitidine Hydrochloride RS in Mobile phase (equivalent to 0.100 mg/mL of ranitidine) Sample solution: Nominally 0.1 mg/mL of ranitidine from Injection in Mobile phase 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 322 nm 

Column: 4.6-mm × 20- to 30-cm; packing L1 

Flow rate: 2 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 1.5 between ranitidine and ranitidine related compound C, System suitability solution 

Column efficiency: NLT 700 theoretical plates, Standard solution 

Tailing factor: NMT 2.0, Standard solution 

Relative standard deviation: NMT 2%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of ranitidine (C₁₃H₂₂N₄O₃S) in the portion of Injection taken:  

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

r_U = peak response of ranitidine from the Sample solution 

r_S = peak response of ranitidine from the Standard solution  

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

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

M_r1 = molecular weight of ranitidine, 314.40 

M_r2 = molecular weight of ranitidine hydrochloride, 350.87 

Acceptance criteria: 90.0%–110.0% 

3 IMPURITIES 

Organic Impurities 

System suitability solution: 1.27 mg/mL of USP Ranitidine Related Compound A RS in methanol 

Standard solution A: 560 µg/mL of USP Ranitidine Hydrochloride RS in water 

Standard solution B: 280 µg/mL of USP Ranitidine Hydrochloride RS from Standard solution A in water 

Standard solution C: 140 µg/mL of USP Ranitidine Hydrochloride RS from Standard solution A in water 

Standard solution D: 84 µg/mL of USP Ranitidine Hydrochloride RS from Standard solution A in water 

Standard solution E: 28 µg/mL of USP Ranitidine Hydrochloride RS from Standard solution A in water 

Standard solution F: 14 µg/mL of USP Ranitidine Hydrochloride RS from Standard solution A in water 

Sample solution: Nominally 25 mg/mL of ranitidine from Injection in water 

[Note—Use Injection of lower concentration without dilution as directed for Application volume.] 

Chromatographic system 

(See Chromatography 〈621〉, Thin-Layer Chromatography.) 

Mode: TLC 

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture 

Application volume: 10 µL 

For the Sample solution, use a volume equivalent to 250 µg of ranitidine. 

Developing solvent system: Ethyl acetate, isopropyl alcohol, ammonium hydroxide, and water (25:15:5:1) 

Visualization: Iodine vapors 

System suitability 

Samples: Apply a volume of Sample solution equivalent to 250 µg of ranitidine. On top of this application, apply 10 µL of the System suitability solution. 

Suitability requirements: Complete resolution between the primary spots of the combined Sample solution and System suitability solution; a spot is observed for Standard solution F in the Analysis. 

Analysis 

Samples: Standard solutions A, B, C, D, E, and F, and Sample solution 

[Note—System suitability sample should also appear on this plate.] 

Allow the spots to dry, and develop the chromatograms until the solvent front has moved NLT 15 cm from the origin. Remove the plate from the chamber, mark the solvent front, and air-dry. Expose the plate to iodine vapor in a closed chamber until the chromatogram is fully revealed. Examine the plate, and compare the intensities of any secondary spots from the Sample solution with those of the principal spots from Standard solutions A, B, C, D, E, and F. 

Acceptance criteria: No secondary spot of the Sample solution is larger or more intense than the principal spot of Standard solution A (2.0%), and no other secondary spot is larger or more intense than the principal spot of Standard solution B (1.0%). The sum of the intensities of all secondary spots from the Sample solution corresponds to NMT 5.0%. 

4 SPECIFIC TESTS 

Particulate Matter in Injections 〈788〉: Meets the requirements for small-volume injections 

Bacterial Endotoxins Test 〈85〉: Contains NMT 7.00 USP Endotoxin Units/mg of ranitidine. 

pH 〈791〉: 6.7–7.3 

Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉 

5 ADDITIONAL REQUIREMENTS 

Change to read: 

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably  of Type I glass. Store below 30°, protected from light. Do not freeze. 

Labeling: Label Injection to state both the content of the active moiety and the content of the salt used in formulating the article. USP Reference Standards 〈11〉 

USP Ranitidine Hydrochloride RS 

USP Ranitidine Related Compound A RS 

5-{[(2-Aminoethyl)thio]methyl}-N,N-dimethyl-2-furanmethanamine, hemifumarate salt. 

C₁₀H₁₈N₂OS. ½ C4H4O4 272.36 

USP Ranitidine Related Compound C RS 

N-{2-[({5-[(Dimethylamino)methyl]-2-furanyl}methyl)sulnyl]ethyl}-N′-methyl-2-nitro-1,1-ethenediamine. 

C₁₃H₂₂N₄O4S 330.40