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Vigabatrin Tablets

DEFINITION

Vigabatrin Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of vigabatrin (C6H11NO2).

IDENTIFICATION

• A. Infrared Absorption

197K

Sample: Grind an appropriate number of Tablets to prepare a 50-mg/mL solution of vigabatrin in water. Pass a portion of the solution 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 pellet using a suitable amount of the residue. Alternatively, the Sample may be prepared by directly mixing an amount of finely ground Tablets (NLT 2) equivalent to about of 3 mg of vigabatrin with about 200 mg of potassium bromide.

Acceptance criteria: The IR spectrum of the Sample is consistent with a similarly prepared pellet of USP Vigabatrin RS.

• B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

ASSAY

• 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: 1.0 mg/mL of USP Vigabatrin RS and 12 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: 1.0 mg/mL of USP Vigabatrin RS in Mobile phase

Sample stock solution: Nominally 5.0 mg/mL of vigabatrin from Tablets (NLT 10) prepared as follows. Transfer a suitable number of Tablets to a suitable volumetric flask. Add Mobile phase to about 80% of the flask volume, and stir for 1 h to give a uniform dispersion of fine particulate. Dilute with Mobile phase to volume, and pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Sample solution: Nominally 1.0 mg/mL of vigabatrin from the Sample stock solution and Mobile phase. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

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: 50 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, 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 Tablets 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: 90.0%–110.0%

PERFORMANCE TESTS

• Dissolution

711

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Mobile phase: Dissolve 6 g of monobasic sodium phosphate in 800 mL of water. Add 100 mL of acetonitrile, and dilute with water to 1 L. Adjust with phosphoric acid to a pH of 2.3.

System suitability solution: 0.6 mg/mL of USP Vigabatrin RS and 6 µg/mL of USP Vigabatrin Related Compound A RS in Mobile phase

Standard solution: L/900 mg/mL of USP Vigabatrin RS in water

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

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: 1.0 mL/min

Injection volume: 50 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 2.0 between vigabatrin related compound A and vigabatrin, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage (Q) of the labeled amount of vigabatrin (C6H11NO2) dissolved:

Result = (rU/rS) × (CS/L) × V × 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)
L	=	= label claim (mg/Tablet)
V	=	= volume of Medium

Tolerances: NLT 75% (Q) of the labeled amount of vigabatrin (C6H11NO2) is dissolved in 30 min.

• Uniformity of Dosage Units

905

: Meet the requirements

IMPURITIES

• 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 finely powdered Tablets (NLT 10) to a suitable volumetric flask. Add Mobile phase to 80% of the flask volume. Sonication may be used to aid in dissolution. Allow the resulting solution to cool to room temperature, and 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 Tablets 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

Name	Relative Retention Time	Relative Response Factora	Acceptance Criteria, NMT (%)
Vigabatrin	0.12	—	—
Vigabatrin related compound Bb	0.13	—	—
Povidonec	0.25	—	—
N-Carboxymethyl vinylpyrrolidinoned	0.38	2.1	0.15
Vigabatrin related compound A	1.0	1.0	0.3
N-3-Oxocarboxypentyl vinylpyrrolidinonee	1.28	1.0	0.15
Any individual unspecified degradation product	—	0.026	0.15
Total impurities	—	—	1.0
a RRF relative to vigabatrin related compound A. b Included for peak identification only. Not to be included in Total impurities as it is controlled in the drug substance. c Povidone is due to excipient. Included for identification only. Not to be included in Total impurities. d 2-(2-Oxo-5-vinylpyrrolidin-1-yl)acetic acid. e 4-Oxo-6-(2-oxo-5-vinylpyrrolidin-1-yl) hexanoic acid.

ADDITIONAL REQUIREMENTS

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

• USP Reference Standards

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

USP38

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Ravi Ravichandran, Ph.D. Principal Scientific Liaison (301) 816-8330	(SM42010) Monographs - Small Molecules 4
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison (301) 816-8106	(GCDF2010) General Chapters - Dosage Forms
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP38–NF33 Page 5778

Pharmacopeial Forum: Volume No. 40(1)