Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Injection for local anaesthesia.
DEFINITION
Bupivacaine Injection is a sterile solution of Bupivacaine Hydrochloride in Water for Injections.
The injection complies with the requirements stated under Parenteral Preparations and with the following requirements.
Content of anhydrous bupivacaine hydrochloride, C18H28N2O,HCl
95.0 to 105.0% of the stated amount.
CHARACTERISTICS
A colourless or almost colourless solution.
IDENTIFICATION
To a volume of the injection containing the equivalent of 25 mg of anhydrous bupivacaine hydrochloride add 2 mL of 13.5M ammonia, shake and filter. Wash the precipitate with water and dry under vacuum at 60° for 16 hours. The infrared absorption spectrum of the dried residue, Appendix II A, is concordant with the reference spectrum of bupivacaine (RS 034).
TESTS
Acidity
pH, 4.0 to 6.5, Appendix V L.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Dilute a volume of the injection, if necessary, to produce a solution containing the equivalent of 0.1% w/v of anhydrous bupivacaine hydrochloride.
(2) Dilute 1 volume of solution (1) to 200 volumes.
(3) 0.00002% w/v of 2,6-dimethylaniline (impurity F).
(4) 0.002% w/v each of bupivacaine impurity B EPCRS and bupivacaine impurity E EPCRS.
(5) Dilute 1 volume of solution (2) to 5 volumes.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (25 cm × 4.6 mm) packed with end-capped ethylene-bridged octadecylsilyl silica gel (5 μm) (X-Bridge BEH C18 is suitable).
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 1 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 240 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
40 volumes of 0.02M potassium dihydrogen orthophosphate, adjusted to pH 8.0 with sodium hydroxide and 60 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to bupivacaine (retention time about 11 minutes) are: impurity E, about 0.25; impurity B, about 0.3 and impurity F, about 0.4.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to impurity E and impurity B is at least 1.5.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to impurity B is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (0.5%);
the area of any peak corresponding to impurity F is not greater than the area of the principal peak in the chromatogram obtained with solution (3) (0.02%);
the area of any other secondary peak is not greater than 0.4 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any secondary peaks, excluding any peak due to impurity F, is not greater than twice the area of the principal peak in the chromatogram obtained with solution (2) (1%).
Disregard any peak, excluding any peak due to impurity F, with an area less than the area of the principal peak in the chromatogram obtained with solution (5) (0.1%).
ASSAY
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in the mobile phase.
(1) Dilute a volume of the injection, if necessary, to produce a solution containing the equivalent of 0.05% w/v of anhydrous bupivacaine hydrochloride.
(2) 0.05% w/v of bupivacaine hydrochloride BPCRS.
(3) 0.002% w/v each of bupivacaine impurity B EPCRS and bupivacaine impurity E EPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between the peaks due to impurity E and impurity B is at least 1.5.
DETERMINATION OF CONTENT
Calculate the content of C18H28N2O,HCl in the injection using the declared content of C18H28N2O,HCl in bupivacaine hydrochloride BPCRS.
LABELLING
The strength is stated in terms of the equivalent amount of anhydrous bupivacaine hydrochloride in a suitable dose-volume.
IMPURITIES
The impurities limited by the requirements of this monograph include impurities B, E and F listed under Bupivacaine Hydrochloride.
