Niacin

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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C₆H₅NO₂            123.11

3-Pyridinecarboxylic acid;

Nicotinic acid CAS RN^®: 59-67-6; UNII: 2679MF687A.

1 DEFINITION

Niacin contains NLT 98.0% and NMT 102.0% of niacin (C₆H₅NO₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Change to read:

B. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 197U _{▲(ERR 1-May-2020)}

Wavelength range: 200-300 nm

Buffer solution: Dissolve 6.8 g of monobasic potassium phosphate in 1000 mL of water. Adjust with 50% sodium hydroxide solution to a pH of 7.0.

Sample solution: 20 µg/mL in Buffer solution

Acceptance criteria: Meets the requirements. The A, A₂₃₉/A₂₆₃ ratio is 0.46-0.52.

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

3 ASSAY

PROCEDURE

Diluent: Methanol and water (82:18)

Mobile phase: Methanol and water (82:18), adjusted with glacial acetic acid to a pH of 3.15 ± 0.05

System suitability solution: 0.25 mg/mL of USP Niacin RS, 0.050 mg/mL of USP 6-Hydroxynicotinic Acid RS, and 0.10 mg/mL of pyridine in Diluent

Standard solution: 0.25 mg/mL of USP Niacin RS in Diluent

Sample solution: 0.25 mg/mL of Niacin in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 260 nm

Column: 4.6-mm x 15-cm; 5-µm packing L8

Flow rate: 1.0 mL/min

Injection volume: 25 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for pyridine, 6-hydroxynicotinic acid, and niacin are about 0.14, 0.64, and 1.0, respectively, System suitability solution.]

Suitability requirements

Resolution: NLT 1.5 between pyridine and 6-hydroxynicotinic acid and NLT 1.5 between 6-hydroxynicotinic acid and niacin, System suitability solution

Relative standard deviation: NMT 2.0% for replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of niacin (C₆H₅NO₂) in the portion of Niacin taken:

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

r_U = peak response of niacin from the Sample solution

r_S = peak response of niacin from the Standard solution 

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

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

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 CHLORIDE AND SULFATE, Chloride (221)

Standard: 0.15 mL of 0.020 N hydrochloric acid

Sample: 0.50 g of Niacin

Acceptance criteria: NMT 0.02%

4.3 CHLORIDE AND SULFATE, Sulfate (221)

Standard: 0.10 mL of 0.020 N sulfuric acid

Sample: 0.50 g of Niacin

Acceptance criteria: NMT 0.02%

4.4 RELATED COMPOUNDS

Solution A: Dissolve 0.6 g of glacial acetic acid in 1 L of water, and adjust with 10% ammonium hydroxide solution to a pH of 5.6.

Solution B: Acetonitrile and methanol (1:1)

Mobile phase: Gradient elution. See Table 1.

Table 1

^a The gradient start time may be adjusted to achieve the required resolution between the 6-methylnicotinic acid and 6,6'-dinicotinic acid peaks of the System suitability solution.

System suitability solution: Transfer 3 mg each of USP 6-Methylnicotinic Acid RS, USP 6,6'-Dinicotinic Acid RS, and pyridine to a 100-mL volumetric flask, dissolve, and dilute with Solution A to volume. Transfer 2.0 mL of the resultant solution to a 5-mL volumetric flask, and dilute with Solution A to volume.

Standard solution: 0.012 mg/mL of USP Niacin RS in Solution A

Sample solution: Transfer 120 mg of Niacin to a 10-mL volumetric flask, add 200 µL of 10% ammonium hydroxide solution, and dilute with Solution A to volume. Shake the flask until the Niacin is completely dissolved.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm x 25-cm; 4-µm packing L1

Column temperature: 15°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for 6-methylnicotinic acid, 6,6'-dinicotinic acid, and pyridine are about 1.0, 1.03, and 1.4, respectively, System suitability solution.]

Suitability requirements

Resolution: NLT 1.5 between 6-methylnicotinic acid and 6,6'-dinicotinic acid peaks, System suitability solution

Relative standard deviation: NMT 10.0% for replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Niacin taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of niacin from the Standard solution

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

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

Acceptance criteria: See Table 2. Disregard any impurity peak less than 0.03%.

Table 2

5 SPECIFIC TESTS

LOSS ON DRYING (731).

Analysis: Dry at 105° for 1 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP 6.6 Dinicotinic Acid RS

USP 6-Hydroxynicotinic Acid RS

USP 6-Methylnicotinic Acid RS

USP Niacin RS