Vigabatrin for Oral Solution

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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1 DEFINITION

Vigabatrin for Oral Solution contains NLT 95.0% and NMT 105.0% of the labeled amount of vigabatrin (C₆H₁₁NO₂).

2 IDENTIFICATION

Change to read:

2.1 A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

Sample: Combine an appropriate number of Vigabatrin for Oral Solution packets to prepare a 50 mg/mL solution of vigabatrin in water. Pass a portion through a suitable filter, and prepare a 2-mg/mL solution by mixing a suitable portion of the filtrate with acetone. Evaporate the solution to dryness in a stream of nitrogen. Prepare a potassium bromide (KBr) pellet using a suitable amount of the residue.

Alternatively, the Sample may be prepared by directly mixing an amount of the contents of NLT 2 packets of Vigabatrin for Oral Solution equivalent to about 3 mg of vigabatrin with about 200 mg of potassium bromide.

Acceptance criteria: The spectrum of the Sample corresponds to that of the spectrum of USP Vigabatrin RS prepared in a similar manner.

2.2 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 in water

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

System suitability solution: 2 mg/mL of USP Vigabatrin RS and 12 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

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

Sample solution: Nominally 2.0 mg/mL of vigabatrin from the contents of NLT 10 Vigabatrin for Oral Solution packets prepared as follows. Combine the contents from the packets, and transfer a suitable amount of the powder equivalent to NLT 200 mg of vigabatrin to a suitable volumetric flask. Dilute with Mobile phase to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 10-µm packing L9
• Flow rate: 1.5 mL/min
• Injection volume: 20 µL

System suitability

• Samples: System suitability solution and Standard solution
• [Note-The relative retention times for vigabatrin related compound A and vigabatrin are about 0.7 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 1.5 between vigabatrin related compound A and vigabatrin peaks, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of vigabatrin (C₆H₁₁NO₂) in the portion of Vigabatrin for Oral Solution taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of vigabatrin from the Sample solution

rₛ = peak response of vigabatrin from the Standard solution

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

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

Acceptance criteria: 95.0%–105.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉: Meets the requirements

5 IMPURITIES

5.1 Organic Impurities

Buffer: 1.5 g/L of ammonium acetate in water

Mobile phase: Acetonitrile and Buffer (5:95)

System suitability solution: 0.1 mg/mL each of USP Vigabatrin RS, USP Vigabatrin Related Compound A RS, USP Vigabatrin Related Compound B RS, and USP Povidone RS in Mobile phase

Sensitivity solution: 0.01 mg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: 0.07 mg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Sample solution: Nominally 22 mg/mL of vigabatrin prepared as follows. Transfer a suitable amount of powder from the combined contents of NLT 10 Vigabatrin for Oral Solution packets, equivalent to NLT 220 mg of vigabatrin, to a suitable volumetric flask. Add Mobile phase to 80% of the volume of the flask. Sonication may be used to aid in dissolution. Allow the resulting solution to cool to room temperature. Dilute with Mobile phase to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Flow rate: 1.0 mL/min
• Injection volume: 10 µL
• Run time: 12 times the retention time of the vigabatrin peak

System suitability

• Samples: System suitability solution, Sensitivity solution, and Standard solution
• [Note-See Table 1 for the relative retention times.]
• Suitability requirements
• Resolution: NLT 2.0 between vigabatrin related compound B and povidone, System suitability solution
• Relative standard deviation: NMT 5.0%, Standard solution
• Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Vigabatrin for Oral Solution taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of each impurity from the Sample solution

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

Cₛ = concentration of USP Vigabatrin Related Compound A in the Standard solution

Cᵤ = nominal concentration of vigabatrin in the Sample solution

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

ᵃ RRF relative to vigabatrin related compound A.

ᵇ Included for peak identification only. Not to be included in Total impurities.

ᶜ Povidone is due to excipient. Included for identification only. Not to be included in Total impurities.

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Povidone RS

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