Naproxen Sodium Tablets

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

Naproxen Sodium Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of naproxen sodium (C₁₄H₁₃NaO₃).

2 IDENTIFICATION

A. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Sodium

Sample: Transfer an amount nominally equivalent to about 250 mg of naproxen sodium from finely powdered Tablets to a centrifuge tube.

Add 12 mL of water and 1 mL of hydrochloric acid. A dense white precipitate is formed. Centrifuge the mixture. Use the clear supernatant for the test.

Acceptance criteria: Meets the requirements

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

C. The UV absorption spectra of the major peak of the Sample solution and that of the Standard solution exhibit maxima and minima at the same wavelengths, as obtained in the Assay.

3 ASSAY

PROCEDURE

Mobile phase: Acetonitrile, water, and glacial acetic acid (450:540:10)

Standard solution: 0.1 mg/mL of USP Naproxen Sodium RS in Mobile phase

Sample stock solution: Nominally 1.0 mg/mL of naproxen sodium from Tablets prepared as follows. Transfer an appropriate amount of naproxen sodium from NLT 20 Tablets, finely powdered, to a suitable volumetric flask. Add 15% of the volume of water and sonicate for 5 min. Add 50% of the volume of Mobile phase and sonicate for an additional 30 min, shaking intermittently. Allow the solution to cool to room temperature and then dilute with Mobile phase to volume. Centrifuge or pass a portion of this solution through a suitable filter..

Sample solution: Nominally equivalent to 0.1 mg/mL of naproxen sodium in Mobile phase from Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm, diode array

Column: 4.6-mm x 15-cm; 5-µm packing L7

Flow rate: 1.2 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of naproxen

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naproxen sodium (C₁₄H₁₃NaO₃) in the portion of Tablets taken:

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

r_U = peak response of naproxen from the Sample solution

r_S = peak response of naproxen from the Standard solution 

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

C_U = nominal concentration of naproxen sodium in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Buffer: 0.1 M of a phosphate buffer with a pH of 7.4, containing 2.62 g/L of monobasic sodium phosphate and 11.50 g/L of anhydrous dibasic sodium phosphate in water

Medium: Buffer, 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: 50 µg/mL of USP Naproxen Sodium RS in Medium

Sample solution: Dilute a filtered portion of the solution under test with Medium as necessary to obtain a nominal concentration of 50 µg/mL of naproxen sodium (C₁₄H₁₃NaO₃).

Instrumental conditions

Mode: UV

Analytical wavelength: About 332 nm (maximum absorbance)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naproxen sodium (C₁₄H₁₃NaO₃) dissolved.

Tolerances: NLT 80% (Q) of the labeled amount of naproxen sodium (C₁₄H₁₃NaO₃) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A: Dissolve 1.36 g of monobasic potassium phosphate in 1 L of water. Adjust with triethylamine to a pH of 6.5. Pass through a suitable filter of 0.45-µm pore size.

Solution B: Acetonitrile

Diluent: Acetonitrile and Solution A (50:50)

Mobile phase: See Table 1.

Table 1
 

Standard stock solution 1: 0.05 mg/mL of USP Naproxen Sodium RS in Diluent

Standard stock solution 2: 0.01 mg/mL of USP Naproxen Related Compound A. RS in methanol

Standard stock solution 3: 0.01 mg/mL of USP Naproxen Related Compound L RS in methanol

System suitability solution: ^▲0.5 µg/mL of USP Naproxen Related Compound ARS from Standard stock solution 2 and 0.5 mg/mL of USP Naproxen Sodium RS in Diluent _{▲(ERR 1-Dec-2018)}

Standard solution: 1.0 µg/mL of USP Naproxen Sodium RS, and 0.5 µg/mL each of USP Naproxen Related Compound A RS and USP Naproxen Related Compound L RS in Diluent, from Standard stock solution 1, Standard stock solution 2, and Standard stock solution 3, respectively

Sample stock solution: Nominally 1.0 mg/ml of naproxen sodium from Tablets prepared as follows. Transfer an appropriate amount of naproxen sodium from NLT 20 Tablets, finely powdered, to a suitable volumetric flask. Add 15% of the volume of water and sonicate for 5 min. Add 50% of the volume of Mobile phase described in the Assay and sonicate for an additional 30 min, shaking intermittently. Allow the solution to cool to room temperature and then dilute with Mobile phase described in the Assay to volume. Centrifuge or pass a portion of this solution through a suitable filter.

Sample solution: Nominally equivalent to 0.55 mg/mL of naproxen sodium in Diluent from the Sample stock solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 236 nm

Column: 4.6-mm x 15-cm, 5-µm packing L7

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 6.0 between naproxen related compound A and naproxen, System suitability solution

Relative standard deviation: NMT 5.0% for naproxen, naproxen related compound A, and naproxen related compound L, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of naproxen related compound A and naproxen related compound L in the portion of Tablets taken:

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

r_U = peak response of naproxen related compound A or naproxen related compound L from the Sample solution

r_S = peak response of naproxen related compound A or naproxen related compound L from the Standard solution

C_S = concentration of USP Naproxen Related Compound A RS or USP Naproxen Related Compound L RS in the Standard solution (mg/mL)

C_U = nominal concentration of naproxen sodium in the Sample solution (mg/mL)

Calculate the percentage of naproxen methyl ester and any individual unspecified degradation product in the portion of Tablets taken:

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

r_U = peak response of naproxen methyl ester or any individual unspecified degradation product from the Sample solution

r_S = peak response of naproxen from the Standard solution

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

C_U = nominal concentration of naproxen sodium in the Sample solution (mg/mL) 

Acceptance criteria: See Table 2. Disregard any peaks below LOQ (0.004% for naproxen methyl ester and any individual unspecified degradation product, 0.002% for naproxen related compound A, and 0.006% for naproxen related compound L.).

Table 2

^a 6-Methoxy-2-naphthoic acid.

^b 1-(6-Methoxynaphthalen-2-yl)ethanone.

^c (S)-Methyl 2-(6-methoxynaphthalen-2-yl)propanoate.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Naproxen Sodium RS

USP Naproxen Related Compound A RS

6-Methoxy-2-naphthoic acid.

C₁₂H₁₀O₃        202.21

USP Naproxen Related Compound L. RS

1-(6-Methoxynaphthalen-2-yl)ethanone.

C₁₃H₁₂O₂            200.23