Folic Acid Tablets

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

Folic Acid Tablets contain NLT 90.0% and NMT 115.0% of the labeled amount of folic acid (C₁₉H₁₉N₇O₆).

2 IDENTIFICATION

A. ULTRAVIOLET ABSORPTION

Sample solution: Digest the quantity of powdered Tablets, equivalent to 100 mg of folic acid, with 100 mL of 0.1 N sodium hydroxide, and filter. Adjust with hydrochloric acid to a pH of 3.0. Cool to 5°, filter, and wash the precipitate of folic acid with cold water until the last washing shows an absence of chloride. Then wash with acetone, and dry at 80° for 1 h. Dissolve the residue in 0.1 N sodium hydroxide to obtain a 10-µg/mL solution.

Acceptance criteria: The UV absorption spectrum of the Sample solution exhibits maxima and minima at the same wavelengths as that of a similar solution of USP Folic Acid RS, concomitantly measured. The absorbance ratio A₂₅₆/A₉₆₅ is 2.80-3.00.

Change to read:

3 ASSAY

3.1 PROCEDURE

Mobile phase: Transfer 35.1 g of sodium perchlorate and 1.40 g of monobasic potassium phosphate to a 1-L volumetric flask. Add 7.0 mL of 1 N potassium hydroxide and 40 mL of methanol, dilute with water to volume, and mix. Adjust with 1 N potassium hydroxide or phosphoric acid to a pH of 7.2.

Diluent: Aqueous solution containing 2 mL of ammonium hydroxide and 1 g of sodium perchlorate per 100 mL

System suitability solution: 0.2 mg/mL each of USP Folic Acid RS and USP Leucovorin Calcium RS (IRA 1-Nov-2022) in Diluent [NOTE-Before use, pass through a filter of 1-µm or finer pore size.]

Standard solution: 0.20 mg/mL of USP Folic Acid RS, corrected for water content in Diluent

Sample solution: Equivalent to 0.2 mg/mL of folic acid, from NLT 20 powdered Tablets in Diluent, shake gently to aid dissolution, and filter, discarding the first portion.

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 25-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 25 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3.6 between leucovorin (IRA 1-Nov-2022) and folic acid, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of folic acid (C₁₉H₁₉N₇O₆) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak area of folic acid from the Sample solution

r_S = peak area of folic acid from the Standard solution

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

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

Acceptance criteria: 90.0%-115.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Medium: Water; 500 mL, deaerated

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: Solution having a known concentration of USP Folic Acid RS, corrected for water content, in Medium

Sample solution: Filtered portion of the solution under test, suitably diluted with the Medium if necessary

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the Assay, making any necessary modifications.

Calculate the percentage of the labeled amount of folic acid (C₁₉H₁₉N₇O₆) dissolved:

Result = (r_U/r_S) x (C_S x D x V/L) x 100

r_U = peak area of folic acid from the Sample solution

r_S = peak area of folic acid from the Standard solution

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

D = dilution factor for the Sample solution

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of folic acid (C₁₉H₁₉N₇O₆) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 ADDITIONAL REQUIREMENTS

5.1 PACKAGING AND STORAGE

Preserve in well-closed containers.

Change to read:

5.2 USP REFERENCE STANDARDS (11)

USP Folic Acid RS

USP Leucovorin Calcium RSA (IRA November 1, 2022)