BP 2025 (Ph. Eur. 11.6 update)
Action and use
Vasodilator; treatment of hypertension.
DEFINITION
Hydralazine Injection is a sterile solution of Hydralazine Hydrochloride in Water for Injections. It is prepared by dissolving Hydralazine Hydrochloride for Injection in the requisite amount of Water for Injections immediately before use. For intravenous infusion, the Hydralazine Hydrochloride for Injection should be dissolved in, and then diluted with, an appropriate volume of a suitable diluent.
The injection complies with the requirements stated under Parenteral Preparations.
STORAGE
Hydralazine Injection deteriorates on storage and should be used immediately after preparation.
HYDRALAZINE HYDROCHLORIDE FOR INJECTION
DEFINITION
Hydralazine Hydrochloride for Injection is a sterile material consisting of Hydralazine Hydrochloride with or without excipients. It is supplied in a sealed container.
The contents of the sealed container comply with the requirements for Powders for Injections or Infusions stated under Parenteral Preparations and with the following requirements.
Content of hydralazine hydrochloride, C8H8N4,HCl
98.0 to 114.0% of the stated amount.
IDENTIFICATION
A. The infrared absorption spectrum, Appendix II A, is concordant with the reference spectrum of hydralazine hydrochloride (RS 177).
B. The light absorption, Appendix II B, in the range 230 to 350 nm of a 0.002% w/v solution exhibits four maxima, at 240, 260, 305 and 315 nm.
C. Yield the reactions characteristic of chlorides, Appendix VI.
TESTS
Acidity
pH of a 2% w/v solution, 3.5 to 4.2, Appendix V L.
Clarity of solution
A 2.0% w/v solution is not more opalescent than reference suspension II, Appendix IV A.
Colour of solution
A 2.0% w/v solution in 0.01M hydrochloric acid is not more intensely coloured than reference solution GY6, Appendix IV B, Method II.
Hydrazine
Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Dissolve the contents of a sealed container in sufficient 0.1M methanolic hydrochloric acid to produce a solution containing 0.5% w/v of Hydralazine Hydrochloride. To 2 mL add 1 mL of a 2% w/v solution of salicylaldehyde in methanol and 0.1 mL of hydrochloric acid, centrifuge and decant the supernatant liquid.
(2) Prepare in the same manner as solution (1), but use 2 mL of a 0.00025% w/v solution of hydrazine sulfate in 0.1M methanolic hydrochloric acid in place of the solution of the material being examined.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel (Merck silica gel 60 plates are suitable).
(b) Use the mobile phase as described below.
(c) Apply 40 μL of each solution.
(d) Develop the plate to 15 cm.
(e) After removal of the plate, dry in air and spray with dimethylaminobenzaldehyde solution R1.
MOBILE PHASE
The upper layer of the mixture obtained by shaking together 20 volumes of 13.5M ammonia, 20 volumes of ethyl acetate and 80 volumes of hexane and allow to stand.
LIMITS
Any spot corresponding to hydrazine in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (2).
Uniformity of content
Sealed containers each containing 20 mg or less of Hydralazine Hydrochloride comply with the requirements stated under Parenteral Preparations, Powders for Injections or Infusions using the following method of analysis. Dissolve the contents of a sealed container in sufficient water to produce 100 mL and dilute a volume containing 1 mg of Hydralazine Hydrochloride to 100 mL with water. Measure the absorbance of the resulting solution at the maximum at 260 nm, Appendix II B. Calculate the content of C8H8N4,HCl taking 535 as the value of A(1%, 1 cm) at the maximum at 260 nm.
ASSAY
Determine the weight of the contents of 10 containers described in the test for uniformity of weight, Appendix XII C1, Powders for Parenteral Use.
Dissolve 0.1 g of the mixed contents of the 10 containers in a mixture of 25 mL of water and 35 mL of hydrochloric acid and titrate with 0.025M potassium iodate VS determining the end point potentiometrically using a platinum indicator electrode and a calomel reference electrode. Each mL of 0.025M potassium iodate VS is equivalent to 4.916 mg of C8H8N4,HCl. Calculate the content of C8H8N4,HCl in a container of average content weight.
STORAGE
The sealed container should be protected from light.
