Naproxen 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 Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of naproxen (C₁₄H₁₄O₃).

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. 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 RS in Mobile phase

Sample stock solution: Nominally equivalent to 1 mg/mL of naproxen in Mobile phase. Transfer an amount equivalent to about 500 mg of naproxen, from NLT 10 finely powdered Tablets, to a 500-mL volumetric flask. Add about 300 mL of Mobile phase, and sonicate for 30 min. Cool to room temperature, and dilute with Mobile phase to volume.

Sample solution: Nominally equivalent to 0.1 mg/mL of naproxen in Mobile phase from Sample stock solution. Pass through a suitable filter of 0.45-µm of pore size.

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

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naproxen (C₁₄H₁₄O₃) 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 RS in the Standard solution (mg/mL) 

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION (711)

Buffer: 0.1 M of pH 7.4 phosphate buffer prepared as follows. Dissolve 2.62 g of monobasic sodium phosphate and 11.50 g of anhydrous dibasic sodium phosphate in 1000 mL of water, and mix.

Medium: Buffer, 900 mL

Apparatus 2: 50 rpm

Time: 45 min

Standard solution: A known concentration of USP Naproxen RS in Buffer

Sample solution: Filter portions of the solution under test, and suitably dilute with Buffer.

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 (C₁₄H₁₄O₃) dissolved.

Tolerances: NLT 80% (Q) of the labeled amount of naproxen (C₁₄H₁₄O₃) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS (905)

Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Buffer: 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.

Diluent: Acetonitrile and Buffer (50:50)

Mobile phase: See Table 1.

Table 1

Standard stock solution 1: Prepare 5 mg/mL of USP Naproxen RS in Diluent. Further dilute this solution with Diluent to obtain 0.05 mg/mL of USP Naproxen 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 A RS from Standard stock solution 2 and 0.5 mg/mL of USP Naproxen RS in Diluent _{▲(ERR 1-Oct-2018)}

Standard solution: 1.0 µg/mL of USP Naproxen RS, 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 solution: Nominally equivalent to 0.5 mg/mL of naproxen from NLT 10 finely powdered Tablets. Transfer nominally equivalent to about 500 mg of naproxen to a 1000-mL volumetric flask. Add 600 mL. of Diluent, and sonicate for 30 min with intermittent shaking. Cool to room temperature, and dilute with Diluent to volume. Mix, and allow to settle for 5 min. Pass through a suitable filter of 0.45-um pore size.

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 Compound L RS in the Standard solution (mg/mL)

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

Calculate the percentage of any other individual impurity in the portion of Tablets taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of any other individual impurity from the Sample solution

r_S = peak response of naproxen from the Standard solution

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

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

F = relative response factor of each individual impurity (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 6-Methoxy-2-naphthoic acid.

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

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

^d Disregard any peaks below LOQ (0.004% for any other individual impurity and naproxen methyl ester, 0.002% for naproxen related compound A, and 0.006% for naproxen related compound L).

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers.

USP REFERENCE STANDARDS (11)

USP Naproxen 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