Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Alpha- and beta-adrenoceptor antagonist.
DEFINITION
Labetalol Injection is a sterile solution of Labetalol Hydrochloride in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of labetalol hydrochloride, C19H24N2O3,HCl
90.0 to 110.0% of the stated amount.
CHARACTERISTICS
A colourless or very pale yellow solution.
IDENTIFICATION
A. Mix a volume containing 50 mg of Labetalol Hydrochloride with 50 mL of 0.1M hydrochloric acid and heat on a water bath for 30 minutes. Cool, filter, add 10 mL of ammonia buffer pH 10.0 and extract with three 15-mL quantities of dichloromethane. Shake the combined extracts with 5 g of anhydrous sodium sulfate, filter and evaporate the filtrate to dryness. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of labetalol (RS 199).
B. The light absorption, Appendix II B, in the range 250 to 400 nm, of a 0.004% w/v solution of the residue obtained in test A in 0.1M sodium hydroxide exhibits a maximum only at 333 nm.
TESTS
Acidity
pH, 3.5 to 4.5, Appendix V L.
Free carboxylic acid and other related substances
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Dilute a volume of the injection containing 80 mg of Labetalol Hydrochloride to about 50 mL with ethanol (96%), evaporate to dryness using a rotary evaporator and dissolve the residue in 1 mL of methanol.
(2) Dilute 1 volume of solution (1) to 200 volumes with methanol.
(3) 0.160% w/v of 5-[1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl]salicylic acid hydrochloride BPCRS in methanol.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F254.
(b) Use the mobile phase as described below.
(c) Apply 20 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry it in a current of warm air, heat at 105° for 30 minutes, cool and examine under ultraviolet light (254 nm).
MOBILE PHASE
5 volumes of 13.5M ammonia, 25 volumes of methanol and 75 volumes of dichloromethane.
LIMITS
In the chromatogram obtained with solution (1):
any spot corresponding to 5-[1-hydroxy-2-(1-methyl-3-phenylpropylamino)ethyl]salicylic acid is not more intense that the spot in the chromatogram obtained with solution (3) (2%);
any other secondary spot is not more intense than the spot in the chromatogram obtained with solution (2) (0.5%).
ASSAY
Dilute a volume containing 50 mg of Labetalol Hydrochloride to 100 mL with water. To 10 mL of the solution add 10 mL of 0.05M sulfuric acid and dilute to 100 mL with water. Measure the absorbance of the resulting solution at the maximum at 302 nm, Appendix II B. Calculate the content of C19H24N2O3,HCl in the injection taking 86 as the value of A(1%, 1 cm) at the maximum at 302 nm.
STORAGE
Labetalol Injection should be protected from light.
