Caffeine and Sodium Benzoate 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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1 DEFINITION

Caffeine and Sodium Benzoate Injection is a sterile solution containing equal amounts of Caffeine and Sodium Benzoate in Water for Injection. It contains NLT 90.0% and NMT 110.0% of the labeled amounts of anhydrous caffeine (C₈H₁₀N₄O₂) and sodium benzoate (C₇H₅NaO₂).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M _{(CN 1-MAY-2020)}

Sample: Use the residue from the Assay for Caffeine.

Acceptance criteria: Meets the requirements

B.

Analysis: Dip the end of a platinum wire into a portion of Injection, and introduce it into a nonluminous flame.

Acceptance criteria: The flame is colored intensely yellow.

C.

Analysis

Part 1: Add a few drops of ferric chloride TS to a 0.5-mL portion of Injection.

Part 2: Add 3 N hydrochloric acid to another portion of Injection.

Acceptance criteria: The criteria in Part 1 and Part 2 must both be met.

Part 1: A salmon-colored precipitate is formed.

Part 2: A white precipitate is formed.

3 ASSAY

3.1 CAFFEINE

Sample solution: A volume of Injection equivalent to 250 mg each of caffeine and sodium benzoate

Analysis: Transfer the Sample solution with the aid of 5 mL of water to a small separator, add 1 drop of phenolphthalein TS, and add 0.1 N sodium hydroxide, dropwise, until a permanent pink color is just produced. Shake the mixture with three or more 20-mL portions of chloroform to effect complete extraction of the caffeine, passing each chloroform extract through a small filter previously moistened with chloroform into a tared dish. Retain the water layer for the Assay for Sodium Benzoate. Wash the stem of the separator, the filter, and the funnel with 10 mL of hot chloroform, adding the washings to the dish. Evaporate the combined chloroform solutions on a steam bath, adding 2 mL of alcohol just before the last trace of chloroform is expelled. Complete the evaporation of the solvent, dry the residue, consisting of caffeine (C₈H₁₀N₄O₂), at 80^o for 4 h. Cool, and weigh.

Acceptance criteria: 90.0%-110.0%

3.2 SODIUM BENZOATE

Sample solution: Use the water layer obtained in the Assay for Caffeine.

Titrimetric system

Mode: Direct titration

Titrant: 0.1 N hydrochloric acid VS

Endpoint detection: Visual

Analysis: Add 75 mL of ether and 5 drops of methyl orange TS to the Sample solution. Titrate with Titrant, and shake vigorously until a permanent pink color is produced in the water layer. Each mL of 0.1 N hydrochloric acid is equivalent to 14.41 mg of sodium benzoate (C₇H₅NaO₂).

Acceptance criteria: 90.0%-110.0%

4 SPECIFIC TESTS

BACTERIAL ENDOTOXINS TEST (85): NMT 0.7 USP Endotoxin Unit/mg of caffeine and sodium benzoate, based on the total, in mg, of the labeled amounts

PH (791): 6.5-8.5

OTHER REQUIREMENTS: It meets the requirements in Injections and Implanted Drug Products (1).

5 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in single-dose containers, preferably of Type I glass.

USP Reference Standards 〈11〉

USP Caffeine RS