Vigabatrin

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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C₆H₁₁NO₂ 129.16

5-Hexenoic acid, 4-amino-;

4-Amino-5-hexenoic acid CAS RN®: 68506-86-5; UNII: GR120KRT6K.

1 DEFINITION

Vigabatrin contains NLT 98.0% and NMT 102.0% of vigabatrin (C₆H₁₁NO₂), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

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

Buffer: 3.4 g/L of monobasic potassium phosphate

Mobile phase: Acetonitrile, methanol, and Buffer (4:40:1000). Adjust with phosphoric acid to a pH of 2.8.

Standard solution: 2.0 mg/mL of USP Vigabatrin RS in Mobile phase

System suitability solution: 12 µg/mL of USP Vigabatrin Related Compound A RS in the Standard solution

Sample solution: 2.0 mg/mL of Vigabatrin in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25.0-cm; 10-µm packing L9
• Flow rate: 1.5 mL/min
• Injection volume: 20 µL
• Run time: NLT 1.8 times the retention time of vigabatrin

System suitability

• Sample: System suitability solution
• [Note-The relative retention times for vigabatrin related compound A and vigabatrin are about 0.5 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between vigabatrin related compound A and vigabatrin
• Relative standard deviation: NMT 1.0% for the vigabatrin peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of vigabatrin (C₆H₁₁NO₂) in the portion of Vigabatrin taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Vigabatrin RS in the Standard solution (mg/mL)

Cᵤ = concentration of Vigabatrin in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

4.1 Limit of γ-Aminobutyric Acid

Solution A: 1.6 g/L of 9-fluorenylmethyl chloroformate (FMOC) in acetone

Buffer A: 4.1 g/L of anhydrous sodium acetate. Adjust with glacial acetic acid to a pH of 4.2.

Buffer B: 31 g/L of boric acid. Adjust with 0.5 g/mL of sodium hydroxide to a pH of 7.7.

Mobile phase: Acetonitrile and Buffer A (32:68)

System suitability stock solution: 2.0 mg/mL of USP Vigabatrin RS and 4 µg/mL of USP γ-Aminobutyric Acid RS in water

System suitability solution: Transfer 1.0 mL of System suitability stock solution to a suitable container. Pipet 2 mL of Buffer B into the container, and mix. Pipet 3 mL of Solution A into the container, mix, and allow to stand for 5 min. Pipet 3 mL of ethyl acetate into the container, shake for a few seconds, and allow the layers to separate. Use the lower layer within 8 h of preparation.

Standard stock solution: 4 µg/mL of USP γ-Aminobutyric Acid RS in water

Standard solution: Transfer 1.0 mL of Standard stock solution to a suitable container. Pipet 2 mL of Buffer B into the container, and mix. Pipet 3 mL of Solution A into the container, mix, and allow to stand for 5 min. Pipet 3 mL of ethyl acetate into the container, shake for a few seconds, and allow the layers to separate. Use the lower layer within 8 h of preparation.

Sample stock solution: 2.0 mg/mL of Vigabatrin in water

Sample solution: Transfer 1.0 mL of Sample stock solution to a suitable container. Pipet 2 mL of Buffer B into the container, and mix. Pipet 3 mL of Solution A into the container, mix, and allow to stand for 5 min. Pipet 3 mL of ethyl acetate into the container, shake for a few seconds, and allow the layers to separate. Use the lower layer within 8 h of preparation.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 263 nm
• Column: 4.6-mm × 15.0-cm; 5-µm packing L11
• Flow rate: 1 mL/min
• Injection volume: 25 µL
• Run time: NLT 1.5 times the retention time of FMOC-vigabatrin

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for (9-fluorenyl)methanol (FMOC-OH), FMOC-γ-aminobutyric acid, and FMOC-vigabatrin are about 0.5, 0.6, and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2.0 between FMOC-OH and FMOC-γ-aminobutyric acid, System suitability solution
• Relative standard deviation: NMT 2.0% for the FMOC-γ-aminobutyric acid peak, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of γ-aminobutyric acid in the portion of Vigabatrin taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of FMOC-γ-aminobutyric acid from the Sample solution

rₛ = peak response of FMOC-γ-aminobutyric acid from the Standard solution

Cₛ = concentration of USP γ-Aminobutyric Acid RS in the Standard stock solution (mg/mL)

Cᵤ = concentration of Vigabatrin in the Sample stock solution (mg/mL)

Acceptance criteria: NMT 0.2% of γ-aminobutyric acid

4.2 Organic Impurities

Buffer: 58.5 g/L of monobasic sodium phosphate in dilute phosphoric acid (23 in 1000)

Mobile phase: Acetonitrile, Buffer, and water (25:25:950)

System suitability solution: 6 µg/mL of USP Vigabatrin Related Compound A RS, 8 µg/mL of USP Vigabatrin Related Compound B RS, 8 µg/mL of USP Vigabatrin Related Compound E RS, and 4.0 mg/mL of USP Vigabatrin RS in Mobile phase

Standard solution: 6 µg/mL of USP Vigabatrin Related Compound A RS, 8 µg/mL of USP Vigabatrin Related Compound B RS, and 8 µg/mL of USP Vigabatrin Related Compound E RS in Mobile phase

Sample solution: 4.0 mg/mL of Vigabatrin in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Columns: Column A and Column B are coupled in series before the Detector.
• Column A: 4.6-mm × 25.0-cm; 5-µm packing L15
• Column B: 4.6-mm × 25.0-cm; 10-µm packing L9
• Flow rate: 1.0 mL/min
• Injection volume: 20 µL
• Run time: NLT 2.2 times the retention time of vigabatrin

System suitability

• Sample: System suitability solution
• [Note-See Table 1 for the relative retention times.]
• Suitability requirements
• Resolution: NLT 1.5 between vigabatrin related compound A and vigabatrin
• Tailing factor: NMT 2.0 each for vigabatrin related compound A and vigabatrin related compound E
• Relative standard deviation: NMT 5.0% for vigabatrin related compound E

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of vigabatrin related compound A, vigabatrin related compound B, or vigabatrin related compound E in the portion of Vigabatrin taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of vigabatrin related compound A, vigabatrin related compound B, or vigabatrin related compound E from the Sample solution

rₛ = peak response of vigabatrin related compound A, vigabatrin related compound B, or vigabatrin related compound E from the Standard solution

Cₛ = concentration of USP Vigabatrin Related Compound A RS, USP Vigabatrin Related Compound B RS, or USP Vigabatrin Related Compound E RS in the Standard solution (mg/mL)

Cᵤ = concentration of Vigabatrin in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Vigabatrin taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any other individual impurity from the Sample solution

rₛ = peak response of vigabatrin related compound E from the Standard solution

Cₛ = concentration of USP Vigabatrin Related Compound E RS in the Standard solution (mg/mL)

Cᵤ = concentration of Vigabatrin in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

ᵃ Sum of all impurities found in the tests for Organic Impurities and Limit of γ-Aminobutyric Acid.

4.3 Residue on Ignition 〈281〉

NMT 0.1%

5 SPECIFIC TESTS

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP γ-Aminobutyric Acid RS

4-Aminobutyric acid.

C₄H₉NO₂ 103.12

USP Vigabatrin RS

USP Vigabatrin Related Compound A RS

5-Vinylpyrrolidin-2-one.

C₆H₉NO 111.14

USP Vigabatrin Related Compound B RS

(E)-2-(2-Aminoethyl)but-2-enoic acid hydrochloride.

C₆H₁₁NO₂ · HCl 165.62

USP Vigabatrin Related Compound E RS

2-(2-Aminobut-3-enyl)malonic acid.

C₇H₁₁NO₄ 173.17