Physostigmine Salicylate

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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C₁₅H₂₁N₃O₂ · C₇H₆O₃      413.47

Pyrrolo[2,3-b]indol-5-ol, 1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethyl-, methylcarbamate (ester), (3aS-cis)-, mono(2-hydroxybenzoate); Physostigmine monosalicylate CAS RN®: 57-64-7; UNII: 2046ZRO9VU.

1 DEFINITION

Physostigmine Salicylate contains NLT 97.0% and NMT 102.0% of physostigmine salicylate (C₁₅H₂₁N₃O₂ · C₇H₆O₃), calculated on the dried basis.

2 IDENTIFICATION

A. Identification—Organic Nitrogenous Bases 〈181〉

Analysis: Use 1 g of sodium bicarbonate instead of 2 mL of 1 N sodium hydroxide.

Acceptance criteria: Meets the requirements

B. Identification Tests—General, Salicylate 〈191〉: Meets the requirements

3 ASSAY

Procedure

Sample: 250 mg of Physostigmine Salicylate

Analysis: Dissolve the Sample in 25 mL of chloroform, and add 25 mL of glacial acetic acid. Titrate with 0.02 N perchloric acid in dioxane VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary correction. Each mL of 0.02 N perchloric acid is equivalent to 8.270 mg of physostigmine salicylate (C₁₅H₂₁N₃O₂ · C₇H₆O₃).

Acceptance criteria: 97.0%–102.0% on the dried basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉

Sample: 100 mg

Acceptance criteria: Negligible

4.2 Sulfate

Sample solution: Precipitate the salicylic acid from 10 mL of a cold, saturated solution of Physostigmine Salicylate with a slight excess of 3 N hydrochloric acid, and filter.

Analysis: Add 5 drops of barium chloride TS to the Sample solution.

Acceptance criteria: No turbidity is produced immediately.

5 SPECIFIC TESTS

5.1 Optical Rotation, Specific Rotation〈781S〉

Sample solution: 10 mg/mL in water

Acceptance criteria: −91° to −94°

5.2 Loss on Drying 〈731〉

Analysis: Dry over silica gel for 24 h.

Acceptance criteria NMT 1.0%

5.3 Readily Carbonizable Substances Test 〈271〉

Sample solution: Dissolve 100 mg in 5 mL of sulfuric acid.

Acceptance criteria: At the end of 5 min, the Sample solution has no more color than Matching Fluid I.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at 25°, excursions permitted between 15° and 30°. 

USP Reference Standards 〈11〉

USP Physostigmine Salicylate RS.