Antipyrine

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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C₁₁H₁₂N₂O          188.23

1,2-Dihydro-1,5-dimethyl-2-phenyl-3H-pyrazol-3-one;

2,3-Dimethyl-1-phenyl-3-pyrazolin-5-one CAS RN: 60-80-0; UNII: T3CHA1B51H

1 DEFINITION

Antipyrine contains NLT 98.0% and NMT 102.0% of antipyrine (C₁₁H₁₂N₂O), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN1-MAY-2020)}

B. 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

Solution A: 0.77 g/L of ammonium acetate in water. Adjust with diluted ammonium hydroxide to a pH of 7.0 and pass through a filter of 0.2-

um pore size.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.12 mg/mL of USP Antipyrine RS and 0.12 µg/mL of USP Antipyrine Related Compound A RS in water

Standard solution: 0.12 mg/ml. of USP Antipyrine RS in water

Sample solution: 0.12 mg/mL of Antipyrine in water

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 2.1-mm x 10-cm; 1.8-µm packing L1

Column temperature: 35°

Flow rate: 0.4 mL/min. Injection volume: 1 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between antipyrine and antipyrine related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of antipyrine (C₁₁H₁₂N₂O) in the portion of Antipyrine taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

C_s = concentration of USP Antipyrine RS in the Standard solution (mg/mL)

C_u = concentration of Antipyrine in the Sample solution (mg/mL)

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

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT.0.15%

ORGANIC IMPURITIES

Buffer: Dissolve 6.8 g of monobasic potassium phosphate in 1 L of water, add 2 mL of triethylamine, and adjust with 5 N sodium hydroxide

solution to a pH of 7.0.

Mobile phase: Methanol and Buffer (43:100)

System suitability solution: 5 µg/mL each of USP Antipyrine RS and USP Antipyrine Related Compound A RS in Mobile phase

Standard solution: 0.5 µg/mL of USP Antipyrine RS and 0.25 µg/mL of USP Antipyrine Related Compound A RS in Mobile phase

Sample solution: 500 µg/mL of Antipyrine in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 6.0-mm x 15-cm; 5-um packing L.1

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: 3 times the retention time of antipyrine

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 3.0 between antipyrine related compound A and antipyrine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of antipyrine related compound A in the portion of Antipyrine taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of antipyrine related compound A from the Sample solution

r_s = peak response of antipyrine related compound A from the Standard solution

C_s = concentration of USP Antipyrine Related Compound A RS in the Standard solution (µg/mL)

C_u = concentration of the Sample solution (µg/mL)

Calculate the percentage of any individual unspecied impurity in the portion of Antipyrine taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of any individual unspecied impurity from the Sample solution

r_s = peak response of antipyrine from the Standard solution

C_s = concentration of USP Antipyrine RS in the Standard solution (µg/mL)

C_u = concentration of the Sample solution (µg/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 60° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Antipyrine RS

USP Antipyrine Related Compound A RS

3-Methyl-1-phenyl-1H-pyrazol-5(4H)-one.

C₁₀H₁₀N₂O            174.20