Levocabastine Hydrochloride

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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C₂₆H₂₉FN₂O₂ · HCl 456.98

4-Piperidinecarboxylic acid, 1-[4-cyano-4-(4-fluorophen yl)cyclohexyl]-3-methyl-4-phenyl-, monohydrochloride, (–)-[1(cis),3α,4β]-; (–)-trans-1-[cis-4-Cyano-4-(p-fluorophenyl)cyclohexyl]-3-methyl-4-phenylisonipecotic acid monohydrochloride CAS RN®: 79547-78-7; UNII: 124XMA6YEI.

1 DEFINITION

Levocabastine Hydrochloride contains NLT 98.5% and NMT 101.5% of C₂₆H₂₉FN₂O₂ · HCl, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

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

C. Optical Rotation, Specific Rotation〈781S〉: Meets the requirements

3 ASSAY

3.1 Procedure

Sample solution: Dissolve 175 mg of Levocabastine Hydrochloride in 50 mL of alcohol, and add 5.0 mL of 0.01 N hydrochloric acid.

Titrimetric system

(See Titrimetry 〈541〉.)

Mode: Direct titration

Titrant: 0.1 N sodium hydroxide VS

Endpoint detection: Potentiometric

3.2 Analysis

Sample: Sample solution

The volume of titrant required to titrate Levocabastine Hydrochloride is the difference between the first and third endpoints. Perform a blank determination and make any necessary correction. Each mL of 0.1 N sodium hydroxide VS is equivalent to 22.85 mg of C₂₆H₂₉FN₂O₂  · HCl.

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

4 IMPURITIES

4.1 Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%, based on a sample weight of about 1.000 g

4.2 Organic Impurities

Procedure

[Note—Prepare solutions immediately before use.]

Diluent: 2 mg/mL of sodium hydroxide in water

Solution A: Dissolve 1.39 g of boric acid in water, and adjust with 1 N sodium hydroxide to a pH of 9.0. Dilute with water to 100 mL.

Run buffer: Dissolve 1.08 g of sodium dodecyl sulfate and 650 mg of hydroxypropyl-β-cyclodextrin in 5 mL of isopropyl alcohol, then dilute with Solution A to 50 mL.

System suitability solution: 12.5 μg/mL of USP Levocabastine Hydrochloride RS and 12.5 μg/mL of USP Levocabastine Related Compound A RS in Diluent Standard solution: Dilute 5.0 mL of the Sample solution with Diluent to 100 mL. Dilute 1.0 mL of this solution with Diluent to 10 mL to obtain a solution containing 12.5 μg/mL of Levocabastine Hydrochloride.

Sample solution: 2.5 mg/mL of Levocabastine Hydrochloride in Diluent

Capillary electrophoresis system

Detector: UV 214 nm

Column: 75-μm × 50-cm uncoated fused-silica capillary column

Column temperature: 50°

Current: See the gradient table below.

[Note—Before performing the System suitability, equilibrate the capillary column with Diluent for 2 min, then equilibrate with Run buffer for at least 5 min.]

System suitability

Sample: System suitability solution

[Note—The relative migration times for levocabastine and levocabastine related compound A are approximately 1.0 and 1.07, respectively.]

Suitability requirements

Resolution: NLT 4 between levocabastine and levocabastine related compound A

[Note—If necessary, adjust the current gradient to achieve the required resolution.]

Analysis

Samples: Diluent (blank), Standard solution, and Sample solution

Separately inject equal volumes (pressure of 3450 Pa for 5 s) of the Samples, and record the peak responses.

[Note—Disregard any peak originating from the Diluent. Disregard any peak with an area of less than 0.1 times the major peak area of the Standard solution (0.05%).]

Acceptance criteria: The area for any peak in the Sample solution, other than the major peak, is not greater than the major peak area of the Standard solution (0.5%); and the sum of all peak areas in the Sample solution, except for the major peak, is not greater than twice the major peak area of the Standard solution (1.0%).

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉: –102° to −106° at 20°

Sample solution: 10 mg/mL in methanol

Loss on Drying 〈731〉: Dry about 1.000 g of the sample at 105° to constant weight: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Protect from light.

USP Reference Standards 〈11〉

USP Levocabastine Hydrochloride RS

USP Levocabastine Related Compound A RS