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Vigabatrin for Oral Solution

DEFINITION

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

IDENTIFICATION

• A. Infrared Absorption

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.

• 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: 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%

PERFORMANCE TESTS

• Uniformity of Dosage Units

905

: Meets 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 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 Soution 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	—	—
Vigabatrin related compound A	1.0	1.0	0.15
Any individual unspecified degradation product	—	0.026	0.15
Total impurities	—	—	0.5
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.

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
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP38–NF33 Page 5777

Pharmacopeial Forum: Volume No. 40(1)