Gabapentin

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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C₉H₁₇NO₂        171.24

Cyclohexaneacetic acid, 1-(aminomethyl)-;

1-(Aminomethyl)cyclohexaneacetic acid CAS RN®: 60142-96-3; UNII: 6CW7F3G59X.

1 DEFINITION

Gabapentin contains NLT 98.0% and NMT 102.0% of gabapentin (C₉H₁₇NO₂), calculated on the anhydrous basis. 

2 IDENTIFICATION

Change to read:

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

Procedure

Diluent: 2.32 g/L of monobasic ammonium phosphate in water. Adjust with phosphoric acid to a pH of 2.0.

Buffer: 0.58 g/L of monobasic ammonium phosphate and 1.83 g/L of sodium perchlorate in water. Adjust with perchloric acid to a pH of 1.8.

Mobile phase: Acetonitrile and Buffer (24:76)

Standard solution: 14.0 mg/mL of USP Gabapentin RS in Diluent

System suitability solution: 2.3 mg/mL of USP Gabapentin RS from the Standard solution in Diluent

Sample solution: 14 mg/mL of Gabapentin in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 5 times the retention time of gabapentin

3.2 System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Column efficiency: NLT 1900 theoretical plates for the gabapentin peak, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of gabapentin (C₉H₁₇NO₂) in the portion of Gabapentin taken:

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

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

4.1 Early-Eluting Organic Impurities

Diluent, Buffer, and Mobile phase: Prepare as directed in the Assay.

System suitability stock solution: 1.4 mg/mL of USP Gabapentin Related Compound A RS and 0.84 mg/mL of USP Gabapentin Related Compound B RS in methanol

System suitability solution: Dissolve a suitable quantity of USP Gabapentin RS in Diluent in a suitable volumetric ask, and add an appropriate volume of System suitability stock solution to obtain a solution containing 14.0 mg/mL of USP Gabapentin RS, 14 µg/mL of USP Gabapentin Related Compound A RS, and 8.4 µg/mL of USP Gabapentin Related Compound B RS in Diluent. Inject within 24 h. Standard solution: 0.0084 mg/mL of USP Gabapentin Related Compound E RS in Diluent

Sample solution: 14 mg/mL of Gabapentin in Diluent. Inject within 24 h.

4.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

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

Temperatures

Autosampler: 5 ± 2°

Column: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 5 times the retention time of gabapentin

4.1.2 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.3 between gabapentin related compound A and gabapentin related compound B, System suitability solution Relative standard deviation: NMT 5.0% for gabapentin related compound E, Standard solution

4.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any impurity in the portion of Gabapentin taken:

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

r_U = peak response of any impurity from the Sample solution

r_S = peak response of gabapentin related compound E from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

^a The relative retention times are calculated based on the retention time of gabapentin.

^b The relative response factors are calculated based on the response of gabapentin related compound E due to the low absorptivity of gabapentin at the monitoring wavelength (215 nm).

4.2 Late-Eluting Organic Impurities

Diluent, Buffer, and Sample solution: Prepare as directed in the Assay.

Mobile phase: Acetonitrile, methanol, and Buffer (35:30:35)

Standard solution: 0.0028 mg/mL of USP Gabapentin Related Compound D RS in Diluent. Initially dissolve USP Gabapentin Related Compound D RS in a small amount of methanol, then dilute with Diluent.

Sample solution: 14 mg/mL of Gabapentin in Diluent

4.2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

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

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 1.5 times the retention time of gabapentin related compound D

4.2.2 System suitability

Sample: Standard solution

Suitability requirements

Column efficiency: NLT 13,600 theoretical plates

Relative standard deviation: NMT 7.0%

4.2.3 Analysis

Samples: Sample solution and Standard solution

[Note—Disregard peaks with a relative retention time of NMT 0.35, relative to gabapentin related compound D.] Calculate the percentage of any impurity in the portion of Gabapentin taken:

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

r_U = peak response of any impurity from the Sample solution

r_S = peak response of gabapentin related compound D from the Standard solution

C_S = concentration of USP Gabapentin Related Compound D RS in the Standard solution (mg/mL)

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

Acceptance criteria

Individual impurities: NMT 0.10%

Total impurities: NMT 0.5% (including impurities found in the test for Early-Eluting Organic Impurities)

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 20 mg/mL in water

Acceptance criteria: 6.5–8.0

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

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Gabapentin RS

USP Gabapentin Related Compound A RS

2-Azaspiro[4.5]decan-3-one.

C₉H₁₅NO      153.22

USP Gabapentin Related Compound B RS

(1-Cyanocyclohexyl)acetic acid.

C₉H₁₃NO₂    167.21

USP Gabapentin Related Compound D RS

[1-(3-Oxo-2-aza-spiro[4.5]dec-2-ylmethyl)cyclohexyl]acetic acid.

C₁₈H₂₉NO₃     307.43

USP Gabapentin Related Compound E RS

Carboxymethylcyclohexanecarboxylic acid.

C₉H₁₄O₄       186.21