Felbamate

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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C₁₁H₁₄N₂O₄ 238.24

1,3-Propanediol, 2-phenyl-, dicarbamate;

2-Phenyl-1,3-propanediol dicarbamate CAS RN^®: 25451-15-4; UNII: X72RBB02N8.

1 DEFINITION

Felbamate contains NLT 98.0% and NMT 102.0% of felbamate (C₁₁H₁₄N₂O₄), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (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.

3 ASSAY

3.1 PROCEDURE

Mobile phase: Acetonitrile, methanol, and water (126:84:790)

Diluent: Acetonitrile, methanol, and water (222:148:630)

System suitability solution: 0.05 mg/mL of USP Felbamate Related Compound A RS and 0.2 mg/mL of USP Felbamate RS in Mobile phase

Standard stock solution: 1.0 mg/mL of USP Felbamate RS prepared as follows. Dissolve a suitable quantity of USP Felbamate RS in 10% of the volumetric flask volume of methanol. Sonicate and shake to completely dissolve, and dilute with Diluent.

Standard solution: 0.2 mg/mL of USP Felbamate RS from Standard stock solution in Mobile phase

Sample stock solution: 1.0 mg/mL of Felbamate prepared as follows. Dissolve a suitable quantity of Felbamate in 10% of the volumetric flask volume of methanol. Sonicate and shake to completely dissolve, and dilute with Diluent.

Sample solution: 0.2 mg/mL of Felbamate from Sample stock solution in Mobile phase

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.8 mL/min

Injection volume: 20 µL

Run time: 3 times the retention time of felbamate

3.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between felbamate related compound A and felbamate, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of felbamate (C₁₁H₁₄N₂O₄) in the portion of Felbamate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of felbamate from the Sample solution

r_S = peak response of felbamate from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 LIMIT OF METHYLCARBAMATE

Mobile phase: Water

Standard solution: 0.1 mg/mL of methylcarbamate in water

Sample solution: Suspend 1 g of Felbamate in 5 mL of water, and mix on a vortex mixer for 1 min followed by sonication for 5 min. Filter the slurry, and use as the Sample solution.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 200 nm

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

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 10%

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: The peak response for methylcarbamate in the Sample solution does not exceed the peak response for methylcarbamate in the Standard solution (0.05%).

4.3 EARLY ELUTING ORGANIC IMPURITIES

Mobile phase, Diluent, Standard stock solution, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 1 µg/mL of USP Felbamate RS in Mobile phase from Standard stock solution

Sample solution: 1.0 mg/mL of Felbamate prepared as follows. Dissolve a suitable quantity of Felbamate in 10% of the volumetric flask volume of methanol. Sonicate and shake to completely dissolve, and dilute with Diluent.

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.0 between felbamate related compound A and felbamate, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 10%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Identify the impurities using the relative retention times shown in Table 1.

Calculate the percentage of each impurity in the portion of Felbamate taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of felbamate from the Standard solution

C_S = concentration of USP Felbamate RS in the Standard solution (µg/mL)

C_U = concentration of Felbamate in the Sample solution (µg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a 2-Phenylpropane-1,3-diol.

^b 3-Carbamoyloxy-2-phenylpropyl allophanate.

^c This impurity is quantified using the test for Late Eluting Organic Impurities.

^d Quantify individual unspecified impurities eluting before felbamate related compound B.

4.4 LATE ELUTING ORGANIC IMPURITIES

Mobile phase: Acetonitrile, methanol, and water (222:148:630)

System suitability solution: 1 µg/mL each of USP Felbamate RS and USP Felbamate Related Compound B RS in Mobile phase

Standard solution: 1 µg/mL of USP Felbamate RS in Mobile phase

Sample solution: 1.0 mg/mL of Felbamate prepared as follows. Dissolve a suitable quantity of Felbamate in 10% of the volumetric flask volume of methanol. Sonicate and shake to completely dissolve, and dilute with Mobile phase.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm x 15-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.8 mL/min

Injection volume: 20 µL

Run time: 10 times the retention time of felbamate

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3 between felbamate and felbamate related compound B, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 10%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Identify the impurities using the relative retention times shown in Table 2.

Calculate the percentage of each impurity in the portion of Felbamate taken:

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

r_U = peak response of each impurity from the Sample solution

r_S = peak response of felbamate from the Standard solution

C_S = concentration of USP Felbamate RS in the Standard solution (µg/mL)

C_U = concentration of Felbamate in the Sample solution (µg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 3,3'-Carbonylbis(oxy)bis(2-phenylpropane-3,1-diyl)dicarbamate.

^b Quantify individual unspecified impurities eluting after felbamate related compound B.

^c Sum of all impurities from Table 1 and Table 2.

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers, and store at room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Felbamate RS

USP Felbamate Related Compound A RS

3-Hydroxy-2-phenylpropyl carbamate.

C₁₀H₁₃NO₃ 195.22

USP Felbamate Related Compound B RS

Phenethyl carbamate.

C₉H₁₁NO₂ 165.19