Methenamine Mandelate

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

Methenamine Mandelate contains NLT 95.5% and NMT 102.0% of methenamine mandelate (C₆H₁₂N₄ · C₈H₈O₃), and contains NLT 50.0% and NMT 53.0% of mandelic acid (C₈H₈O₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

3 ASSAY

Procedure

Sample solution: Transfer 60 mg of Methenamine Mandelate to a 250-mL conical flask. Add 15 mL of dehydrated alcohol, stir to dissolve, and add 40 mL of chloroform.

Titrimetric system

Mode: Direct titration

Titrant: 0.05 N silver nitrate in dehydrated alcohol prepared as follows. Dissolve by stirring 8.5 g of silver nitrate in 1000 mL of dehydrated alcohol. Transfer 100 mg of sodium chloride, previously dried at 110° for 2 h, to a 100-mL beaker, and dissolve in 50 mL of water. Titrate

with the silver nitrate solution to the potentiometric endpoint, using a silver billet indicator electrode and a silver–silver chloride double-junction reference electrode containing a potassium nitrate salt bridge. Calculate the normality of the titrant.

Endpoint detection: Potentiometric

Analysis: Titrate the Sample solution with Titrant, determining the endpoint potentiometrically, using a silver billet indicator electrode and a silver–silver chloride double-junction reference electrode containing a potassium nitrate salt bridge. Each mL of 0.05 N silver nitrate is equivalent to 7.308 mg of methenamine mandelate (C₆H₁₂N₄ · C₈H₈O₃).

Acceptance criteria: 95.5%–102.0% on the dried basis

4 OTHER COMPONENTS

Content of Mandelic Acid

Sample solution: Transfer 90 mg to a 250-mL conical flask containing 50 mL of water. When the solution is complete, titrate the magnetically stirred solution.

Titrimetric system

Mode: Direct titration

Titrant: 0.05 N ceric ammonium nitrate VS

Endpoint detection: Potentiometric

Analysis: Titrate the Sample solution with Titrant, determining the endpoint potentiometrically. Each mL of 0.05 N ceric ammonium nitrate is

equivalent to 3.804 mg of mandelic acid (C₈H₈O₃).

Acceptance criteria: 50.0%–53.0% on the dried basis

5 IMPURITIES

Residue on ignition 〈281〉: NMT 0.1%

Chloride and Sulfate, Chloride〈221〉

Sample: 1.0 g

Analysis: Dissolve the Sample in 10 mL of water, and add gradually 500 mg of anhydrous sodium carbonate. Evaporate to dryness, and ignite the residue at a dull-red heat. Add 20 mL of 2 N nitric acid, stir gently, and filter.

Acceptance criteria: 0.01%; the filtrate shows no more chloride than corresponds to 0.15 mL of 0.020 N hydrochloric acid.

Sulfate

Sample: 0.20 g

Analysis: Dissolve the Sample in 10 mL of water. Add 5 drops of 3 N hydrochloric acid and 5 drops of barium chloride TS.

Acceptance criteria: No turbidity appears within 1 min.

6 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry over silica gel for 18 h.

Acceptance criteria: NMT 1.5%

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Methenamine Mandelate RS