Ascorbic Acid 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

Ascorbic Acid Injection is a sterile solution, in Water for Injection, of Ascorbic Acid prepared with the aid of Sodium Hydroxide, Sodium Carbonate, or Sodium Bicarbonate. It contains NLT 90.0% and NMT 110.0% of the labeled amount of ascorbic acid (C₆H₈O₆).

2 IDENTIFICATION

A.

Analysis: To a volume of Injection, equivalent to 40 mg of ascorbic acid, add 4 mL of 0.1 N hydrochloric acid, then add 4 drops of methylene blue TS, and warm to 40°.

Acceptance criteria: The deep blue color becomes appreciably lighter or is completely discharged within 3 min.

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

C. The Injection imparts an intense yellow color to a nonluminous flame.

3 ASSAY

Change to read:

3.1 PROCEDURE

Mobile phase: Dissolve 15.6 g of dibasic sodium phosphate and 12.2 g of monobasic potassium phosphate in 2000 mL of water, and adjust with phosphoric acid to a pH of 2.5 ± 0.05.

Standard solution: 0.5 mg/mL of USP Ascorbic Acid RS in Mobile phase. [NOTE-Refrigerate and store protected from light until use. The solution is stable for at least 24 h. Inject within 3 h after removal from the refrigerator.]

Sample solution: Dilute the Injection, if necessary, with Mobile phase to obtain a solution with a concentration of about 0.5 mg/mL. [NOTE-Refrigerate and store protected from light until use. The solution is stable for at least 24 h. Inject within 3 h after removal from the refrigerator.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 245 nm

Column: 15-cm (ERR 1-Jul-2022) × 6-mm; packing L39

Flow rate: 0.6 mL/min

Injection volume: 4 µL

System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 3500 theoretical plates

Tailing factor: NMT 1.6

Relative standard deviation: NMT 1.5%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of ascorbic acid (C₆H₈O₆) in the portion of Injection taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 IMPURITIES

4.1 LIMIT OF OXALATE

Analysis: Dilute a volume of Injection, equivalent to 50 mg of ascorbic acid, with water to 5 mL. Add 0.2 mL of acetic acid and 0.5 mL of calcium chloride TS.

Acceptance criteria: No turbidity is produced in 1 min.

5 SPECIFIC TESTS

PH (791): 5.5-7.0

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

BACTERIAL ENDOTOXINS TEST (85): It contains NMT 1.2 USP Endotoxin Units/mg of ascorbic acid.

6 ADDITIONAL REQUIREMENTS

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

LABELING: In addition to meeting the requirements in Labeling (7), Labels and Labeling for Injectable Products, fused-seal containers of the Injection in concentrations of 250 mg/mL and greater are labeled to indicate that since pressure may develop on long storage, precautions should be taken to wrap the container in a protective covering while it is being opened.

USP REFERENCE STANDARDS (11)

USP Ascorbic Acid RS