Phenoxybenzamine Capsules

General Notices

Action and use

Alpha-adrenoceptor antagonist.

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 107.5% of the stated amount.

Identification

A. Dissolve a quantity of the contents of the capsules containing 40 mg of Phenoxybenzamine Hydrochloride in 50 mL of ethanol-free chloroform, wash the solution with three 20-mL quantities of 0.01m hydrochloric acid, filter the chloroform solution and dilute 10 mL of the filtrate to 50 mL with ethanol-free chloroform. The light absorption of the resulting solution, Appendix II B, in the range 230 to 350 nm exhibits two maxima, at 272 nm and 279 nm.
B. Carry out the method for thin-layer chromatography, Appendix III A, using the following solutions.
(1) Shake a quantity of the capsule contents with methanol. Add sufficient methanol to produce a solution containing 0.1% w/v of Phenoxybenzamine Hydrochloride and filter (A Whatman GF/C filter is suitable).
(2) 0.1% w/v of phenoxybenzamine hydrochloride BPCRS in methanol.
chromatographic conditions
(a) Use as the coating silica gel F254 (Merck silica gel 60 F254 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).
C. The contents of the capsules yield reaction A characteristic of chlorides, Appendix VI.

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

The chromatographic conditions described under Related substances may be used.

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 in acetonitrile.

(1) Dissolve a quantity of the contents of the capsules to produce a solution containing 0.08% w/v of Phenoxybenzamine Hydrochloride.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) Dilute 1 volume of solution (2) to 10 volumes.
(4) 0.08% w/v of phenoxybenzamine hydrochloride BPCRS.
(5) To 10 mL of solution (4) add 0.5 mL of 0.1m sodium hydroxide.
chromatographic conditions
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with octylsilyl silica gel for chromatography (5 µm) (HiChrom Kromasil C8 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 25°.
(e) Use a detection wavelength of 268 nm.
(f) Inject 10 µL of each solution.
(g) Allow the chromatography to proceed for three times the retention time of phenoxybenzamine.
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 relative retention with reference to phenoxybenzamine (retention time = about 11 minutes) is: phenoxybenzamine tertiary amine, about 0.2.

system suitability

The test is not valid unless, in the chromatogram obtained with solution (5), the resolution factor between the peaks due to phenoxybenzamine and the secondary peak with a relative retention of about 1.3 is at least 4.0.

limits

In the chromatogram obtained with solution (1):

the area of any peak corresponding to phenoxybenzamine tertiary amine 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 all the 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

Carry out the method for liquid chromatography, Appendix III D, using the following solutions in acetonitrile.

(1) Weigh five capsules. Open the capsules carefully without loss of shell material, remove the contents, wash the shells with three 10-mL quantities of acetonitrile and add the washings to the capsules contents. Add sufficient acetonitrile to produce 200 mL and mix with the aid of ultrasound for 30 minutes, swirling occasionally. Add sufficient acetonitrile to produce a solution containing 0.02% w/v of Phenoxybenzamine Hydrochloride. Allow the shells to dry at room temperature to constant weight. The difference between the weights represents the weight of the total contents.
(2) 0.02% w/v of phenoxybenzamine hydrochloride BPCRS.
(3) To 10 mL of solution (1) add 0.5 mL of 0.1m sodium hydroxide.
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 factor between the peaks due to phenoxybenzamine and the secondary peak with a relative retention of about 1.3 is at least 4.0.

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 phenoxybenzamine tertiary amine.