Caffeine Citrate Oral Solution

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

1 DEFINITION

Caffeine Citrate Oral Solution is a sterile aqueous solution containing Caffeine and citric acid. It contains NLT 90.0% and NMT 110.0% of the labeled amount of caffeine citrate (C₁₄H₁₈N₈O₉). It contains no bacteriostat or other preservative.

2 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, Citrate 191): Meets the requirements

C.

Solution A: Transfer 4 g of potassium iodide to a 100-mL volumetric flask, and add 10 mL of water. Shake until the potassium iodide is dissolved. Add 2 g of iodine to the volumetric flask, and shake until dissolved. Dilute with water to volume.

Sample solution: 5.0 mL of Oral Solution

Analysis: Transfer the Sample solution to a 25-ml centrifuge tube, and add 5 drops of Solution A. Add 0.5 mL of 2.0 M hydrochloric acid.

Acceptance criteria: A brown precipitate that dissolves on neutralization with 0.5 mL of sodium hydroxide TS is produced.

3 ASSAY

PROCEDURE

Mobile phase: Acetonitrile, tetrahydrofuran, and 0.01 M sodium acetate (5:4:191) adjusted with glacial acetic acid to a pH of 4.5

Theophylline stock solution: 0.02 mg/mL of theophylline in water

Standard solution: 0.2 mg/ml. of USP Caffeine RS and 0.004 mg/ml. of theophylline from Theophylline stock solution in water

Sample solution: Nominally 0.4 mg/mL of caffeine citrate (equivalent to 0.2 mg/mL of caffeine) from Oral Solution in water prepared as follows. Transfer a volume of Oral Solution, equivalent to 50 mg of caffeine, to a 250-mL volumetric flask. Dilute with water to volume, pass through a polyvinylidene difluoride or equivalent membrane of 0.45-µm pore size, and use the filtrate.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 275 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[NOTE-See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 6.0 between theophylline and caffeine

Tailing factor: NMT 2.0 each for the theophylline and caffeine

Relative standard deviation: NMT 2.0% for caffeine

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration (C_A), in mg/mL, of caffeine citrate in the Sample solution:

Result = (r_u /r_s ) × C_s × (M_r1 /M_r2 )

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Caffeine RS in the Standard solution (mg/mL)

M_r1 = molecular weight of caffeine citrate, 386.31

M_r2 = molecular weight of caffeine, 194.19

Calculate the percentage of the labeled amount of caffeine citrate (C₁₄H₁₈N₈O₉) in the portion of Oral Solution taken:

Result = (C_A /C_u ) × 100

C_A = concentration of caffeine citrate in the Sample solution

C_u = nominal concentration of caffeine citrate in the Sample solution

Acceptance criteria: 90.0%–110.0%

4 IMPURITIES

ORGANIC IMPURITIES

Mobile phase, Theophylline stock solution, Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay

Sensitivity solution: 5 µg/mL of caffeine and 0.1 µg/mL of theophylline from the Standard solution in water

System suitability

Sample: Sensitivity solution

Suitability requirements

Sensitivity: The theophylline peak is discernible.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oral Solution taken:

Result = (r_u /r_s ) × (C_s /C_A ) × (M_r1 /M_r2 ) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of caffeine from the Standard solution

C_s = concentration of USP Caffeine RS in the Standard solution (mg/mL)

C_A = concentration of caffeine citrate in the Sample solution as determined in the Assay

M_r1 = molecular weight of caffeine citrate, 386.31

M_r2 = molecular weight of caffeine, 194.19

F = relative response factor, (see Table 1)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

Sterility Tests 〈71〉: It meets the requirements of the Test for Sterility of the Product to Be Examined, Membrane Filtration.

pH 〈791〉: 4.2–5.2

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose, tight containers, and store at a temperature between 15°–30°.

USP Reference Standards 〈11〉

USP Caffeine RS