Edition: BP 2025 (Ph. Eur. 11.6 update)
General Notices
Action and use
Skeletal muscle relaxant.
DEFINITION
Baclofen Oral Solution is a solution of Baclofen in a suitable aqueous vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements.
Content of baclofen, C10H12ClNO2
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 a mixture of 35 volumes of acetonitrile and 65 volumes of water.
(1) Dilute a volume of the oral solution containing 5 mg of Baclofen to 100 mL.
(2) 0.005% w/v of baclofen BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 5 μL of each solution.
(d) Develop the plate to 10 cm.
(e) After removal of the plate, dry in air.
(f) Place an evaporating dish containing 4 mL of water, 1 mL of 7M hydrochloric acid and 0.5 g of potassium permanganate in a chromatography tank, close the tank and allow to stand for 2 minutes. Place the plate in the tank, close the tank and leave the plate in contact with the vapour for 1 minute.
(g) After removal of the plate, place it in a current of cold air until an area of coating below the line of application shows only a faint blue colour on the addition of 0.05 mL of potassium iodide and starch solution. Spray the plate with potassium iodide and starch solution and examine in daylight.
MOBILE PHASE
20 volumes of glacial acetic acid, 20 volumes of water and 80 volumes of butan-1-ol.
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 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
Impurity A
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute a weighed quantity of the oral solution containing 5 mg of Baclofen to 50 mL.
(2) 0.0002% w/v of baclofen impurity A EPCRS.
(3) 0.01% w/v of baclofen BPCRS, 0.0003% w/v of propyl 4-hydroxybenzoate, 0.0003% w/v of methyl 4-hydroxybenzoate and 0.0002% w/v of baclofen impurity A EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Assay may be used.
MOBILE PHASE
5 g of sodium dodecyl sulfate in a mixture of 5 mL of orthophosphoric acid and 650 mL of water and diluted to 1000 mL with acetonitrile R1.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to methyl-4-hydroxybenzoate and impurity A (lactam) and between the peaks due to impurity A and propyl-4-hydroxybenzoate is at least 5.0.
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) (2%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute a weighed quantity of the oral solution containing 5 mg of Baclofen to 50 mL.
(2) 0.01% w/v of baclofen BPCRS.
(3) 0.01% w/v of baclofen BPCRS, 0.0003% w/v of propyl 4-hydroxybenzoate and 0.0002% w/v of baclofen impurity A EPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatograph (10 μm) (Nucleosil C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.5 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 218 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
5 g of sodium dodecyl sulfate in a mixture of 5 mL of orthophosphoric acid and 650 mL of water and diluting to 1000 mL with acetonitrile R1.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity A and propyl-4-hydroxybenzoate is at least 5.0.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C10H12ClNO2, weight in volume, using the declared content of C10H12ClNO2 in baclofen BPCRS.
STORAGE
Baclofen Oral Solution should be stored below 25° and protected from light. It should not be refrigerated.
