Edition: BP 2025 (Ph. Eur. 11.6 update)
NOTE: This monograph has been developed to cover unlicensed formulations.
Action and use
Antituberculosis drug.
DEFINITION
Ethambutol Oral Solution is a solution of Ethambutol Hydrochloride in a suitable flavoured aqueous vehicle.
The oral solution complies with the requirements stated under Oral Liquids and with the following requirements. Where appropriate, the oral solution also complies with the requirements stated under Unlicensed Medicines.
Content of ethambutol hydrochloride, C10H24N2O2,2HCl
95.0 to 105.0% of the stated amount.
IDENTIFICATION
A. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the principal peak in the chromatogram obtained with solution (2).
B. To 10 mL of the oral solution add 2 mL of a 1% w/v solution of copper(II) sulfate followed by 1 mL of 1M sodium hydroxide; a blue colour is produced.
TESTS
2-Aminobutan-1-ol
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Dilute a quantity of the oral solution containing 0.5 g of Ethambutol Hydrochloride to 10 mL with methanol.
(2) 0.05% w/v of 2-aminobutan-1-ol in methanol.
(3) Equal volumes of solutions (1) and (2).
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel G.
(b) Use the mobile phase as described below.
(c) Apply 2 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, allow it to dry in air, heat at 110° for 10 minutes and cool; spray with ninhydrin solution R1 and heat at 110° for 5 minutes.
MOBILE PHASE
10 volumes of 13.5M ammonia, 15 volumes of water and 75 volumes of methanol.
SYSTEM SUITABILITY
The test is not valid unless the chromatogram obtained with solution (3) shows two clearly separated spots.
LIMITS
In the chromatogram obtained with solution (1):
any spot corresponding to 2-aminobutan-1-ol is not more intense that the spot in the chromatogram obtained with solution (2) (1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) Dilute a weighed quantity of the oral solution containing 80 mg of Ethambutol Hydrochloride with sufficient of a mixture of 10 volumes of acetonitrile R1 and 90 volumes of water to produce 100 mL.
(2) 0.08% w/v of ethambutol hydrochloride BPCRS in a mixture of 10 volumes of acetonitrile and 90 volumes of water
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (12.5 cm × 4.6 mm) packed with octadecylsilyl silica gel for chromatography (5 μm) (ACE Excel Super C18 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 a column temperature of 40°.
(e) Use a detection wavelength of 210 nm.
(f) Inject 10 μL of each solution.
When the chromatograms are recorded under the prescribed conditions, the retention time of ethambutol is about 2.3 minutes.
MOBILE PHASE
10 volumes of acetonitrile R1 and 90 volumes of a 0.21% w/v solution of potassium dihydrogen orthophosphate containing 0.1% w/v of triethylamine.
DETERMINATION OF CONTENT
Determine the weight per mL of the oral solution, Appendix V G, and calculate the content of C10H24N2O2,2HCl, weight in volume, using the declared content of C10H24N2O2,2HCl in ethambutol hydrochloride BPCRS.
IMPURITIES
The impurity limited by the requirements of this monograph is: 2-aminobutan-1-ol.
