Fingolimod 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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C₁₉H₃₃NO₂ · HCl 343.93

1,3-Propanediol, 2-amino-2-[2-(4-octylphenyl)ethyl]-, hydrochloride;

2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride CAS RN®: 162359-56-0. Fingolimod (free base)

C₁₉H₃₃NO₂ 307.48 CAS RN®: 162359-55-9.

1 DEFINITION

Fingolimod Hydrochloride contains NLT 98.0% and NMT 102.0% of fingolimod hydrochloride (C₁₉H₃₃NO₂ · HCl), calculated on an anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or 197M (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.

C. Identification Tests - General 〈191〉, Chemical Identification Tests, Chloride

3 ASSAY

3.1 Procedure

Solution A: 0.1% phosphoric acid in water

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Solution A (1:1)

Standard solution: 0.6 mg/mL of USP Fingolimod Hydrochloride RS in Diluent

Sample solution: 0.6 mg/mL of Fingolimod Hydrochloride in Diluent

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 3-mm × 15-cm; 3-μm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 5 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Relative standard deviation: NMT 0.73%

Tailing factor: NMT 5

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of fingolimod hydrochloride (C₁₉H₃₃NO₂ · HCl) in the portion of Fingolimod Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on an anhydrous and solvent-free basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Solution A, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.6 mg/mL of USP Fingolimod System Suitability Mixture RS in Diluent

Standard stock solution: Use the Standard solution from the Assay.

Standard solution: 0.003 mg/mL of USP Fingolimod Hydrochloride RS from the Standard stock solution in Diluent

Sensitivity solution: 0.3 μg/mL of USP Fingolimod Hydrochloride RS from the Standard solution in Diluent

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[Note - The relative retention times of fingolimod and O-acetyl fingolimod are about 1.00 and 1.11, respectively.]

Suitability requirements

Resolution: NLT 1.2 between O-acetyl fingolimod and fingolimod nonyl homolog; NLT 0.8 between 2-phenethyl fingolimod analog and 3-phenethyl fingolimod analog, System suitability solution

Relative standard deviation: NMT 10%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each individual impurity in the portion of Fingolimod Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak area of each impurity from the Sample solution

r_S = peak area of fongolimod hydrochloride from the Standard solution

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

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

F = relative response factor for each individual impurity (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.5%

Microbial Enumeration Tests 〈61〉 and Tests for Specified Microorganisms 〈62〉: The total aerobic microbial count is NMT 103 cfu/g. The total combined molds and yeasts count is NMT 102 cfu/g.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store below 30° in a dry place.

USP Reference Standards 〈11〉

USP Fingolimod Hydrochloride RS

USP Fingolimod System Suitability Mixture RS

It contains Fingolimod Hydrochloride and small amounts of the following impurities:

O-Acetyl fingolimod;

2-Amino-2-(hydroxymethyl)-4-(4-octylphenyl)butyl acetate.

C₂₁H₃₅NO₃ 349.51

Fingolimod decyl homolog;

2-Amino-2-(4-decylphenethyl)propane-1,3-diol. C₂₁H₃₇NO₂ 335.53

Fingolimod heptyl homolog;

2-Amino-2-(4-heptylphenethyl)propane-1,3-diol. C₁₈H₃₁NO₂ 293.45

Fingolimod hexyl homolog;

2-Amino-2-(4-hexylphenethyl)propane-1,3-diol. C₁₇H₂₉NO₂ 279.42

Fingolimod nonyl homolog;

2-Amino-2-(4-nonylphenethyl)propane-1,3-diol. C₂₀H₃₅NO₂ 321.51

2-Phenethyl fingolimod analog;

2-Amino-2-[4-octyl-2-(4-octylphenethyl)phenethyl]propane-1,3-diol. C₃₅H₅₇NO₂ 523.85

3-Phenethyl fingolimod analog;

2-Amino-2-[4-octyl-3-(4-octylphenethyl)phenethyl]propane-1,3-diol. C C₃₅H₅₇NO₂ 523.85