Meloxicam

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

Meloxicam contains NLT 98.0% and NMT 102.0% of meloxicam (C₁₄H₁₃N₃O₄S₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

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

3 ASSAY

Procedure

Solution A: Mixture of a 0.1% (w/v) solution of ammonium acetate adjusted with 10% ammonia solution to a pH of 9.1

Mobile phase: Methanol and Solution A (21:29)

Diluent: Methanol and 1 N sodium hydroxide (250:1)

System suitability solution: 0.08 mg/mL each of USP Meloxicam RS and USP Meloxicam Related Compound A RS prepared as follows.

Dissolve USP Meloxicam RS and USP Meloxicam Related Compound A RS in 50% of the flask volume of Diluent, and dilute with water to volume.

Standard solution: 0.2 mg/mL of USP Meloxicam RS prepared as follows. Dissolve USP Meloxicam RS in 50% of the flask volume of Diluent, and dilute with water to volume.

Sample solution: 0.2 mg/mL of Meloxicam prepared as follows. Dissolve Meloxicam in 50% of the flask volume of Diluent, and dilute with water to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 360 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for meloxicam related compound A and meloxicam are 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between meloxicam related compound A and meloxicam, System suitability solution

Tailing factor: NMT 2.0 for the meloxicam peak, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of meloxicam (C₁₄H₁₃N₃O₄S₂) in the portion of Meloxicam taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of meloxicam from the Sample solution

r_S = peak response of meloxicam from the Standard solution

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

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities, Procedure 1

Perform either Procedure 1 or Procedure 2, depending on the manufacturing process used.

Solution A: 0.1% (w/v) solution of monobasic potassium phosphate adjusted with 1 N sodium hydroxide to a pH of 6.0

Solution B: Methanol

Diluent: Methanol and 1 N sodium hydroxide (50:3)

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.08 mg/mL each of USP Meloxicam RS, USP Meloxicam Related Compound A RS, and USP Meloxicam Related

Compound B RS prepared as follows. Dissolve USP Meloxicam RS, USP Meloxicam Related Compound A RS, and USP Meloxicam Related

Compound B RS in 10% of the flask volume of Diluent, and dilute with water to volume.

Standard stock solution: 0.6 mg/mL of USP Meloxicam RS prepared as follows. Dissolve USP Meloxicam RS in 25% of the flask volume of Diluent, and dilute with methanol to volume.

Standard solution: 0.012 mg/mL of USP Meloxicam RS in methanol from the Standard stock solution

Sample solution: 4 mg/mL of Meloxicam prepared as follows. Dissolve Meloxicam in 25% of the flask volume of Diluent, and dilute with methanol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 260 and 350 nm (variable wavelength or multi-wavelength detector)

Column: 4.6-mm × 15-cm; 5-μm packing L1

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 5 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times are listed in Table 2.]

Suitability requirements

Resolution: NLT 3.0 between meloxicam related compound A and meloxicam at 350 nm; NLT 3.0 between meloxicam related compound B and meloxicam at 260 nm, System suitability solution

Relative standard deviation: NMT 10%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of meloxicam at 350 nm from the Standard solution

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

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

F = relative response factor (see Table 2)

[Note—For the specified impurities, calculate the percentage content of each impurity, using the peak responses from the Sample solution recorded at the detection wavelength given in Table 2. For an unknown impurity, calculate the percentage content, using peak responses recorded at the wavelength that gives the greater response.]

Acceptance criteria: See Table 2.

Table 2

^a 5-Methylthiazol-2-amine.

^b Ethyl 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide.

^c N-[3,5-Dimethylthiazol-2(3H]-ylidene)-4-hydroxy-2-methyl-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide.

^d N-[3-Ethyl-5-methylthiazol-2(3H)-ylidene]-4-hydroxy-2-methyl-2H-benzo[e][1,2]thiazine-3-carboxamide 1,1-dioxide.

Organic Impurities, Procedure 2

If an article complies with this test, the labeling indicates that it meets the requirements under Organic Impurities, Procedure 2.

Solution A and Solution B: Proceed as directed in Procedure 1.

Mobile phase: See Table 3.

Table 3

Diluent A: Diluent B and 0.4 N sodium hydroxide (50:3)

Diluent B: Methanol and water (2:3)

Standard stock solution A: 0.01 mg/mL of USP Meloxicam RS prepared as follows. Dilute a solution of 0.05 mg/mL of USP Meloxicam RS in Diluent A with Diluent B.

Standard stock solution B: 0.05 mg/mL each of USP Meloxicam Related Compound B RS and USP Meloxicam Related Compound C RS prepared as follows. Transfer suitable amounts of USP Meloxicam Related Compound B RS and USP Meloxicam Related Compound C RS to an adequate volumetric flask. Add 0.4 N sodium hydroxide to 6% of the flask volume, and sonicate for 2 min. Add an additional 40% of the flask volume of methanol, sonicate for 2 min, and dilute with water to volume.

Standard solution: 0.001 mg/mL of USP Meloxicam RS and 0.0015 mg/mL each of USP Meloxicam Related Compound B RS and USP

Meloxicam Related Compound C RS prepared as follows. Transfer suitable volumes of Standard stock solution A and Standard stock solution B to an adequate volumetric flask, and dilute with Diluent B to volume.

Sample solution: 1 mg/mL of Meloxicam prepared as follows. Dissolve a suitable amount of Meloxicam with 50% of the flask volume of Diluent A, and dilute with Diluent B to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV variable wavelength or multi-wavelength detector at 260 and 350 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Column temperature: 45°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

[Note—The relative retention times are listed in Table 4.]

Suitability requirements

Relative standard deviation: NMT 5.0% for meloxicam, meloxicam related compound B, and meloxicam related compound C

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Meloxicam 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 the corresponding related compound from the Standard solution

C_S = concentration of the corresponding USP Related Compound RS in the Standard solution (mg/mL). [Note—Use the concentration of USP Meloxicam RS for unknown impurities.]

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

[Note—Use the peak response and concentration of USP Meloxicam RS for unknown impurities; for the specified impurities, calculate the percentage content of each impurity using the Sample solution peak responses recorded at the detection wavelength given in Table 4. For an unknown impurity, calculate the percentage content using peak responses recorded at the wavelength that gives the greater response.]

Acceptance criteria: See Table 4.

Table 4

^a 5-Methylthiazol-2-amine.

^b Isopropyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

Labeling: The labeling states with which Procedure under Organic Impurities the article complies if a test other than Procedure 1 is used.

USP Reference Standards 〈11〉

USP Meloxicam RS

USP Meloxicam Related Compound A RS