Piroxicam

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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C₁₅H₁₃N₃O₄S 331.35

2H-1,2-Benzothiazine-3-carboxamide, 4-hydroxy-2-methyl-N-2-pyridinyl-, 1,1-dioxide;

4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide CAS RN®: 36322-90-4; UNII: 13T4O6VMAM.

1 DEFINITION

Piroxicam contains NLT 97.0% and NMT 103.0% of piroxicam (C₁₅H₁₃N₃O₄S).

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M. Do not dry specimens.

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B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U

Solution: 10 μg/mL

Medium: Hydrochloric acid in methanol (1 in 1200)

Acceptance criteria: Meets the requirements (USP 1-Dec-2020)

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C. Thin-Layer Chromatography 〈201〉

Diluent: Chloroform and methanol (1:1)

Standard solution: 1 mg/mL of USP Piroxicam RS in Diluent

Sample solution: 1 mg/mL in Diluent

Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.)

Absorbent: 0.25-mm layer of chromatographic silica gel

Application volume: 20 μL

Developing solvent system: Toluene and glacial acetic acid (95:5)

Analysis

Samples: Standard solution and Sample solution

Allow the spots to dry, and develop the chromatogram in the Developing solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, and air-dry. Place the plate in the developing chamber, and develop as before. Remove the plate from the chamber, mark the solvent front, and air-dry. Locate the spots on the plate by viewing under short-wavelength UV light.

Acceptance criteria: The R value of the principal spot of the Sample solution corresponds to that of the Standard solution. (USP 1-Dec-2020)

Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay (USP 1-Dec-2020)

3 ASSAY

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Procedure

Solution A: Mix 1 mL of phosphoric acid with 1000 mL of water.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Methanol

Standard solution: 0.05 mg/mL of USP Piroxicam RS in Diluent. Sonicate to dissolve, if needed.

Sample solution: 0.05 mg/mL of Piroxicam in Diluent. Sonicate to dissolve, if needed.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 340 nm

Column: 4.6-mm × 15-cm; 3.5-μm packing L1

Temperatures

Autosampler: 4°

Column: 35°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0% (USP 1-Dec-2020)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of piroxicam (C₁₅H₁₃N₃O₄S) in the portion of Piroxicam taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of piroxicam from the Sample solution

r_S = peak response of piroxicam from the Standard solution

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

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

Acceptance criteria: 97.0%–103.0%

4 IMPURITIES

Add the following:

Limit of Piroxicam Related Compound B

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1000 μg/mL of USP Piroxicam RS and 10 μg/mL each of USP Piroxicam Related Compound B RS and USP Piroxicam Related Compound G RS in Diluent. Sonicate to dissolve, if needed. Use freshly prepared solution.

Standard solution: 2 μg/mL of USP Piroxicam Related Compound B RS in Diluent. Sonicate to dissolve, if needed. Use freshly prepared solution.

Sample solution: 1.0 mg/mL of Piroxicam in Diluent. Sonicate to dissolve, if needed. Use freshly prepared solution.

System suitability

Samples: System suitability solution and Standard solution

[Note - The relative retention times for piroxicam related compound B, piroxicam related compound G, and piroxicam are 0.89, 0.95, and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between piroxicam related compound B and piroxicam related compound G, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of piroxicam related compound B in the portion of Piroxicam taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of piroxicam related compound B from the Sample solution

r_S = peak response of piroxicam related compound B from the Standard solution

C_S = concentration of USP Piroxicam Related Compound B RS in the Standard solution (μg/mL)

C_U = concentration of Piroxicam in the Sample solution (μg/mL)

Acceptance criteria: NMT 0.2% (USP 1-Dec-2020)

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Organic Impurities

Solution A: 0.5% of glacial acetic acid in water. Adjust with ammonium hydroxide to a pH of 6.2.

Solution B: Acetonitrile

Mobile phase: See Table 2.

Table 2

Sensitivity solution: 0.5 μg/mL of USP Piroxicam RS in methanol. Sonicate to dissolve, if needed. Use freshly prepared solution.

Standard solution: 2 μg/mL each of USP Piroxicam RS, USP Piroxicam Related Compound A RS, USP Piroxicam Related Compound D RS, USP Piroxicam Related Compound G RS, and USP Piroxicam Related Compound J RS in methanol. Sonicate to dissolve, if needed. Use freshly prepared solution.

Sample solution: 1.0 mg/mL of Piroxicam in methanol. Sonicate to dissolve, if needed. Use freshly prepared solution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm for quantitation of piroxicam, piroxicam related compound A, piroxicam related compound D, and any unspecified impurity; UV 355 nm for quantitation of piroxicam related compound G, and piroxicam related compound J

Column: 4.6-mm × 15-cm; 3.5-μm packing L1

Temperatures

Autosampler: 4°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: Sensitivity solution and Standard solution

Suitability requirements

Resolution: NLT 5.0 between piroxicam and piroxicam related compound G, Standard solution

Relative standard deviation: NMT 5.0% for piroxicam and piroxicam related compounds A, D, G, and J; Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of piroxicam related compounds A, D, G, and J in the portion of the Piroxicam taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of piroxicam related compound A, D, G, or J from the Sample solution

r_S = peak response of piroxicam related compound A, D, G, or J from the Standard solution

C_S = concentration of the corresponding Reference Standard in the Standard solution (μg/mL)

C_U = concentration of Piroxicam in the Sample solution (μg/mL)

Calculate the percentage of any unspecified impurity in the portion of the Piroxicam taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any unspecified impurity from the Sample solution

r_S = peak response of piroxicam from the Standard solution

C_S = concentration of USP Piroxicam RS in the Standard solution (μg/mL)

C_U = concentration of Piroxicam in the Sample solution (μg/mL)

Acceptance criteria: See Table 3.

Table 3

^a Methyl 4-hydroxy-2H-benzothiazine-3-carboxylate 1,1-dioxide

^b For peak identification only; quantitated by the test for Limit of Piroxicam Related Compound B.

^c Total impurities is the sum of piroxicam related compound B from the test for Limit of Piroxicam Related Compound B and each specified and any unspecified impurities from the Organic Impurities test.

Residue on Ignition 〈281〉: NMT 0.3%

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Change to read:

USP Reference Standards 〈11〉

USP Piroxicam RS

USP Piroxicam Related Compound A RS

Pyridin-2-amine.

C₅H₆N₂ 94.11

USP Piroxicam Related Compound B RS

4-Hydroxy-N-(pyridin-2-yl)-2H-benzothiazine-3-carboxamide 1,1-dioxide.

C₁₄H₁₁N₃O₄S 317.32

USP Piroxicam Related Compound D RS

Methyl 2-[1,1-dioxido-3-oxobenzoisothiazol-2(3H)-yl]acetate.

C₁₀H₉NO₅S 255.25

USP Piroxicam Related Compound G RS

Methyl 4-hydroxy-2H-benzothiazine-3-carboxylate 1,1-dioxide monohydrate.

C₁₀H₉NO₅S · H₂O 273.26

USP Piroxicam Related Compound J RS

Methyl 4-hydroxy-2-methyl-2H-benzothiazine-3-carboxylate 1,1-dioxide.

C₁₁H₁₁NO₅S 269.27