Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Antiepileptic.
DEFINITION
Gabapentin Oral Solution contains Gabapentin.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of gabapentin, C9H17NO2
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions in methanol.
(1) Dilute a quantity of the oral solution to produce a solution containing 0.025% w/v of Gabapentin.
(2) 0.025% w/v of gabapentin EPCRS.
(3) 0.025% w/v each of gabapentin EPCRS and vigabatrin BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel.
(b) Use the mobile phase as described below.
(c) Apply 10 μL of each solution.
(d) Develop the plate to 8 cm.
(e) After removal of the plate, dry at 105°, spray with ninhydrin solution R4 and heat at 105° for 2 minutes. Examine in daylight.
MOBILE PHASE
2 volumes of methanol, 3 volumes of acetonitrile and 15 volumes of 0.05M potassium dihydrogen orthophosphate, adjusted to pH 6.3 with potassium hydroxide solution.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
B. In the Assay, the principal peak in the chromatogram obtained with solution (1) shows a peak with the same retention time as the principal peak in the chromatogram obtained with solution (2).
TESTS
Acidity or alkalinity
pH, 6.0 to 7.5, Appendix V L.
Gabapentin impurity A
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in water.
(1) Dilute a quantity of the oral solution to produce a solution containing 0.25% w/v of Gabapentin.
(2) 0.001% w/v of gabapentin impurity A EPCRS.
(3) 0.05% w/v of each of methyl 4-hydoxybenzoate and gabapentin impurity A EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (5 cm × 2.0 mm) packed with end-capped octadecylsilyl silica gel for chromatography (1.7 μm) (Kinetex C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 0.4 mL per minute.
(d) Use a column temperature of 40°.
(e) Use a detection wavelength of 210 nm.
(f) Inject 1.5 μL of each solution.
MOBILE PHASE
95 volumes of acetonitrile R1 and 405 volumes of a 0.154% w/v solution of ammonium acetate in water.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to methyl 4-hydrozybenzoate and gabapentin impurity A is not less than 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity A is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.4%).
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in mobile phase A.
(1) Dilute a quantity of the oral solution to produce a solution containing 0.5% w/v of Gabapentin.
(2) Dilute 1 volume of solution (1) to 100 volumes and dilute 1 volume of the resulting solution to 10 volumes.
(3) 0.05% w/v each of gabapentin EPCRS and gabapentin impurity B EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 2.0 mm) packed with end-capped phenylethyl silica gel for chromatography (4 μm) (Synergi Polar RP is suitable).
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use a column temperature of 50°.
(e) Use evaporative light scattering detection using a flow rate of 1.3 litres per minute and an evaporator temperature of 60°.
(f) Inject 20 μL of each solution.
MOBILE PHASE
Mobile phase A 0.063% w/v of ammonium formate in water, adjusted to pH 3.2 with formic acid.
Mobile phase B acetonitrile.
| Time ( Minutes) |
Mobile Phase A (% v/v) |
Mobile Phase B (% v/v) |
Comment |
| 0-1
1-7 7-8 8-9 9-18 |
99
99→40 40 40→99 99 |
1
1→60 60 60→1 1 |
isocratic
linear gradient isocratic linear gradient re-equilibration |
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to
gabapentin and impurity B is not less than 6.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any secondary peak is not greater than the area of the principal peak in the chromatogram obtained with
solution (2) (0.1%);
the sum of the areas of all the secondary peaks is not greater than 10 times the area of the principal peak if the
chromatogram obtained with solution (2) (1.0%);
Disregard any peak with an area less than half the area of the principal peak in the chromatogram obtained with solution
(2) (0.05%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a weighed quantity of the oral solution with sufficient water to produce a solution containing 0.25% w/v of Gabapentin.
(2) 0.25% w/v of gabapentin EPCRS in water.
(3) 0.25% w/v of gabapentin EPCRS and 0.06% w/v of methyl parahydroxybenzoate in water.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (Eclipse XDB C-18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 211 nm.
(f) Inject 5 μL of each solution.
MOBILE PHASE
2.5 volumes of orthophosphoric acid, 200 volumes of acetonitrile R1 and 800 volumes of 0.006M sodium heptanesulfonate.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to gabapentin and methyl parahydroxybenzoate is at least 10.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C9H17NO2, weight in volume, using the declared content of C9H17NO2 in gabapentin EPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities A and B listed under Gabapentin.
