Pentamidine Isethionate

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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C₁₉H₂₄N₄O₂ · (C₂H₆O₄S)₂     592.68

Ethanesulfonic acid, 2-hydroxy-, compd. with 4,4'-[1,5-pentanediylbis(oxy)]bis [benzenecarboximidamide]; 4,4'-(Pentane-1,5-diylbis(oxy))dibenzimidamide bis(2-hydroxyethanesulfonate) CAS RN®: 140-64-7; UNII: V2P3K60DA2.

1 DEFINITION

Pentamidine Isethionate contains NLT 98.5% and NMT 101.5% of C₁₉H₂₄N₄O₂ · (C₂H₆O₄S)₂, calculated on the dried basis. 

2 IDENTIFICATION

Change to read:

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

B. Oxygen-Flask Combustion 〈471〉

Barium chloride solution: 60 mg/mL of barium chloride in water

Analysis: Burn 150 mg, using 10 mL of 3% Hydrogen peroxide as the absorbing liquid. When the process is complete, acidify with 1 mL of diluted hydrochloric acid, and add 1 mL of the Barium chloride solution.

Acceptance criteria: A white precipitate is formed.

C. The retention time of the pentamidine isethionate peak of the Sample solution corresponds to that of the Standard solution, as obtained in the test for Organic Impurities.

3 ASSAY

Procedure

Sample solution: 5 mg/mL in dimethylformamide. Add 0.25 mL of thymol blue TS.

Analysis: Titrate under a stream of nitrogen with 0.1 M tetrabutylammonium hydroxide VS, determining the endpoint until the color changes to intense blue. Perform a blank determination, and make any necessary correction (see Titrimetry 〈541〉). Each mL of 0.1 M tetrabutylammonium hydroxide is equivalent to 29.63 mg of C₁₉H₂₄N₄O₂ · (C₂H₆O₄S)₂.

Acceptance criteria: 98.5%–101.5% on the dried basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉

Acceptance criteria: NMT 0.1% on a 1-g sample

Organic Impurities

Procedure

Buffer: 30 mg/mL of ammonium acetate in water, adjusted with triethylamine to a pH of 7.5

Mobile phase: Methanol and Buffer (65:35)

System suitability solution: Prepare 40.0 mL of a 2.5 mg/mL solution of USP Pentamidine Isethionate RS in water. Adjust with 0.2 M sodium hydroxide to a pH of 10.5, and boil under reflux for 20 min. Cool, and dilute with water to 50.0 mL. Transfer quantitatively 1 mL of this solution to a 50-mL volumetric ask, and dilute with Mobile phase to volume.

Standard solution: 2 µg/mL of USP Pentamidine Isethionate RS in Mobile phase

Sample solution: 1.0 mg/mL of Pentamidine Isethionate in Mobile phase. [Note—It must be demonstrated that the nal product does not contain a detectable amount of alkyl 2-hydroxyethanesulphonates, a potential in-process impurity.]

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 265 nm

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

Flow rate: 1 mL/min

Injection size: 10 µL

Run time: 3.5 times the retention time of pentamidine

4.2 System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 2 between the two major peaks.

[Note—The chromatogram shows two major peaks.]

4.3 Analysis

Samples: Standard solution and Sample solution

Acceptance criteria

Individual impurities: NMT 0.4%. [Note—Exclude any other peak producing a response of less than 0.02%.] Total impurities: NMT 0.7%

5 SPECIFIC TESTS

pH 〈791〉: 4.5–6.5, in a carbon dioxide-free aqueous solution containing 50 mg/mL of Pentamidine Isethionate

Loss on Drying 〈731〉: Dry at 105°: it loses NMT 4.0% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at controlled room temperature. • USP Reference Standards 〈11〉

USP Pentamidine Isethionate RS

C₁₉H₂₄N₄O₂ · (C₂H₆O₄S)₂