Edition: BP 2025 (Ph. Eur. 11.6 update)
Action and use
Alpha-adrenoceptor antagonist; treatment of hypertension in phaeochromocytoma.
DEFINITION
Phenoxybenzamine Capsules contain Phenoxybenzamine Hydrochloride.
The capsules comply with the requirements stated under Capsules and with the following requirements.
Content of phenoxybenzamine hydrochloride, C18H22ClNO,HCl
92.5 to 105.0% of the stated amount.
IDENTIFICATION
A. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions prepared in
methanol.
(1) Shake a quantity of the powdered capsule contents containing 10 mg of Phenoxybenzamine Hydrochloride with 5 mL with methanol. Dilute to 10 mL and filter (a Whatman GF/C filter is suitable).
(2) 0.1% w/v of phenoxybenzamine hydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use as the coating silica gel F (Merck silica gel 60 plates are suitable).
(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 in air and spray with dilute potassium iodobismuthate solution.
MOBILE PHASE
20 volumes of dichloromethane and 80 volumes of acetone.
CONFIRMATION
The principal spot in the chromatogram obtained with solution (1) corresponds in position and colour to that in the chromatogram obtained with solution (2).
B. In the Assay, the retention time of the principal peak in the chromatogram obtained with solution (1) is similar to that of the peak in the chromatogram obtained with solution (2).
TESTS
Dissolution
Comply with the requirements in the dissolution test for tablets and capsules, Appendix XII B1.
TEST CONDITIONS
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
(b) Use 500 mL of 0.01M hydrochloric acid, at a temperature of 37°, as the medium.
PROCEDURE
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with 0.01M hydrochloric acid if necessary, to produce a solution expected to contain 0.002% w/v of Phenoxybenzamine Hydrochloride.
(2) 0.002% w/v of phenoxybenzamine hydrochloride BPCRS in 0.01M hydrochloric acid.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (Kromasil C8 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 268 nm.
(f) Inject 10 µL of each solution.
MOBILE PHASE
45 volumes of a 0.22% w/v solution of anhydrous sodium dihydrogen orthophosphate, previously adjusted to pH 3.0 with orthophosphoric acid, and 55 volumes of acetonitrile.
When the chromatograms are recorded under the prescribed conditions, the retention time of phenoxybenzamine is about 11 minutes.
DETERMINATION OF CONTENT
Calculate the total content of phenoxybenzamine hydrochloride, C18H22ClNO,HCl, in the medium from the chromatograms obtained and using the declared content of C18H22ClNO,HCl in phenoxybenzamine hydrochloride BPCRS.
LIMITS
The amount of phenoxybenzamine hydrochloride released is not less than 75% (Q) of the stated amount.
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions prepared in acetonitrile.
(1) Shake a quantity of the capsule contents containing 80 mg of Phenoxybenzamine Hydrochloride with 50 mL and dilute to 100 mL.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) Dilute 1 volume of solution (2) to 10 volumes.
(4) Add 0.5 mL of 0.1M sodium hydroxide to 10 mL of 0.08% w/v of phenoxybenzamine hydrochloride BPCRS in acetonitrile (generation of impurity B and impurity 1).
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used with a flow rate of 0.6 mL per minute. For solution (1), allow the chromatography to proceed for 1.5 times the retention time of phenoxybenzamine.
When the chromatograms are recorded under the prescribed conditions, the relative retentions with reference to phenoxybenzamine (retention time about 35 minutes) are: impurity B, about 0.1 and impurity 1, about 0.15.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between the peaks due to impurity B and impurity 1 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 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%);
the area of any peak corresponding to impurity 1 is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any other secondary peak is not greater than 4 times the area of the principal peak in the chromatogram obtained with solution (3) (0.4%);
the sum of the areas of any other secondary peaks is not greater than 1.5 times the area of the principal peak in the chromatogram obtained with solution (2) (1.5%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).
ASSAY
Weigh the contents of 20 capsules. Mix and powder if necessary. Carry out the method for liquid chromatography, Appendix III D, using the following solutions in acetonitrile.
(1) Mix, with the aid of ultrasound and occasional swirling, a quantity of the capsule contents containing 50 mg of Phenoxybenzamine Hydrochloride with 30 mL of acetonitrile. Dilute to produce 50 mL and filter. Dilute 1 volume of the filtrate to 5 volumes.
(2) 0.02% w/v of phenoxybenzamine hydrochloride BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Dissolution may be used.
DETERMINATION OF CONTENT
Calculate the content of C18H22ClNO,HCl in the capsules using the declared content of C18H22ClNO,HCl in phenoxybenzamine hydrochloride BPCRS.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Phenoxybenzamine Hydrochloride and:
1. 2-(benzyl-[1-phenoxypropan-2-yl]amino)amine.
