Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Barbiturate.
DEFINITION
Phenobarbital Elixir is an oral solution containing 0.3% w/v of Phenobarbital in a suitable flavoured vehicle containing a sufficient volume of ethanol (96 %) or of an appropriate Dilute Ethanol to give a final concentration of 38% v/v of ethanol.
The elixir complies with the requirements stated under Oral Liquids and with the following requirements.
Content of phenobarbital, C12H12N2O3
0.285 to 0.315% w/v.
IDENTIFICATION
Extract 50 mL with three 50-mL quantities of ether, wash the combined ether extracts with 20 mL of water, discard the washings, extract the ether solution with a mixture of 5 mL of 2M sodium hydroxide and 25 mL of water and then with two 5-mL quantities of water. Acidify the combined aqueous extracts to litmus paper with 2M hydrochloric acid, extract with four 25-mL quantities of ether, wash the combined ether extracts with two 2-mL quantities of water, wash the combined aqueous washings with 10 mL of ether, add the ether washings to the combined ether extracts, evaporate the ether and dry the residue of phenobarbital to constant weight at 105°. The infrared absorption spectrum of the residue Appendix II A, is concordant with the reference spectrum of phenobarbital (RS 270).
TESTS
Ethanol content
36 to 40% v/v, Appendix VIII F.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dilute a quantity of the elixir containing 100 mg of Phenobarbital in 100 mL of the mobile phase.
(2) Dilute 1 volume of solution (1) to 10 volumes with the mobile phase. Dilute 1 volume of the resulting solution to 50 volumes with the mobile phase.
(3) 0.0005% w/v of phenobarbital impurity A EPCRS and 0.0005% w/v of phenobarbital impurity B EPCRS in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb S5 ODS 2 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
(g) Allow the chromatography to proceed for twice the run time of phenobarbital.
MOBILE PHASE
25 volumes of acetonitrile and 75 volumes of a solution containing 0.66% w/v of sodium acetate in water, adjusted to pH 4.5 using glacial acetic acid.
When the chromatograms are recorded under the prescribed conditions the retention times relative to phenobarbital (retention time, about 9 minutes) are: impurity A, about 0.4; impurity B, about 0.5.
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 impurity B is at least 1.5.
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) (0.2%);
the sum of the areas of all secondary peaks is not greater than 2.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.5%).
Disregard any peak with an area less than 0.5 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in the mobile phase.
(1) Dissolve a weighed quantity of the elixir containing 100 mg of Phenobarbital in 100 mL of the mobile phase. Dilute 1 volume of the resulting solution to 10 volumes with the mobile phase.
(2) 0.01% of phenobarbital BPCRS in the mobile phase.
(3) A solution of 0.0005% w/v of phenobarbital impurity A EPCRS and 0.0005% w/v of phenobarbital impurity B EPCRS
in the mobile phase.
CHROMATOGRAPHIC CONDITIONS
Use the chromatographic conditions described under the test for Related substances.
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 impurity B is at least 1.5.
DETERMINATION OF CONTENT
Determine the weight per mL of the elixir, Appendix V G, and calculate the content of C12H12N2O3, weight in volume, using the declared content of C12H12N2O3 in phenobarbital BPCRS.
STORAGE
Phenobarbital Elixir should be protected from light.
