Pentoxifylline

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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C₁₃H₁₈N₄O₃ 278.31

1H-Purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl)-;

1-(5-Oxohexyl)theobromine CAS RN^®: 6493-05-6.

1 DEFINITION

Pentoxifylline contains NLT 98.0% and NMT 102.0% of pentoxifylline (C₁₃H₁₈N₄O₃).

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-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

3.1 PROCEDURE

Solution A: 1 g/L of perchloric acid

Mobile phase: Methanol, tetrahydrofuran, acetonitrile, and Solution A (2:2.5:15:80)

System suitability solution: 0.024 mg/mL of caffeine and 0.048 mg/mL of USP Pentoxifylline RS in Mobile phase

Standard solution: 0.05 mg/mL of USP Pentoxifylline RS in Mobile phase

Sample solution: 0.05 mg/mL of Pentoxifylline in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 273 nm

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

Flow rate: 0.7 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 10.0 between caffeine and pentoxifylline, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of pentoxifylline (C₁₃H₁₈N₄O₃) in the portion of Pentoxifylline taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0%

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 CHLORIDE AND SULFATE, Chloride (221)

Sample: 2.0 g

Acceptance criteria: The Sample shows no more chloride than corresponds to 0.31 mL of 0.020 N hydrochloric acid (0.011%).

4.3 CHLORIDE AND SULFATE, Sulfate (221)

Sample: 1.0 g

Acceptance criteria: The Sample shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (0.02%).

4.4 ORGANIC IMPURITIES

Solution A and Mobile phase: Prepare as directed in the Assay.

System suitability solution: 0.7 µg/mL of caffeine and 350 µg/mL of USP Pentoxifylline RS in Mobile phase

Standard solution: 0.7 µg/mL of USP Pentoxifylline RS in Mobile phase

Sample solution: 350 µg/mL of Pentoxifylline in Mobile phase

Chromatographic system: Proceed as directed in the Assay except for the following:

Injection volume: 20 µL

Run time: NLT 5 times the retention time for pentoxifylline

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 10.0 between caffeine and pentoxifylline, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Measure the areas of all the peaks in the Sample solution, except for that of pentoxifylline.

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

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of pentoxifylline from the Standard solution

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

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

Acceptance criteria

Individual impurities: NMT 0.2%

Total impurities: NMT 0.5%

5 SPECIFIC TESTS

5.1 COMPLETENESS OF SOLUTION (641)

Sample solution: 1 g in 50 mL of carbon dioxide-free water

Acceptance criteria: Meets the requirements

5.2 ACIDITY

Sample solution: 1 g in 50 mL of carbon dioxide-free water

Analysis: To the Sample solution add 1 drop of bromothymol blue TS.

Acceptance criteria: NMT 0.2 mL of 0.01 N sodium hydroxide is required to produce a color change.

5.3 LOSS ON DRYING (731)

Analysis: Dry under vacuum at 60° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers.

6.2 USP REFERENCE STANDARDS (11)

USP Pentoxifylline RS