Medium: 0.1 N hydrochloric acid; 500 mL.

Apparatus 1: 100 rpm.

Time: 45 minutes.

Procedure— Determine the amount of C18H22ClNO·HCl dissolved from UV absorbances at the wavelength of maximum absorbance at about 267 nm on filtered portions of the solution under test, suitably diluted with Dissolution Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Phenoxybenzamine Hydrochloride RS in the same Medium.

Tolerances— Not less than 75% (Q) of the labeled amount of C18H22ClNO·HCl is dissolved in 45 minutes.

procedure for content uniformity—

Buffer solution, Mobile phase, System suitability solution, and Chromatographic system— Proceed as directed in the Assay.

Standard solution— Proceed as directed for Standard preparation in the Assay.

Test solution— Use the Assay preparation.

Procedure— Proceed as directed in the Assay. Calculate the percentage of each individual impurity by the formula: in which F is the relative response factor, which is 1.1 for the known degradant phenoxybenzamine tertiary amine and 1 for all other individual impurities; ri is the peak response for the individual impurity obtained from the Test solution; and rs is the sum of all the peak responses obtained from the Test solution. Not more than 0.5% of phenoxybenzamine tertiary amine is found; not more than 0.1% of any other specified or unspecified individual impurity (degradant) is found; and not more than 0.5% total of all the specified and unspecified impurities is found.

Buffer solution— Dissolve 1.1 g of anhydrous monobasic sodium phosphate in 500 mL of water. Adjust with concentrated phosphoric acid to a pH of 3.0.

Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (45:55).

Standard preparation— Prepare a solution of USP Phenoxybenzamine Hydrochloride RS in acetonitrile having a known concentration of 0.2 mg per mL. Sonicate for 5 minutes to mix well.

System suitability solution— Prepare a solution of 0.5 mL of 0.1 N sodium hydroxide and 10 mL of the Standard preparation taken in a vial. [note—Basic solutions of phenoxybenzamine hydrochloride will produce the known degradant tertiary amine phenoxybenzamine (the second major peak that elutes before the phenoxybenzamine peak and has a relative retention time of about approximately 0.3 minutes) and an unknown related substance. Severe degradation of the drug substance will be observed if the solution is allowed to stand for more than 1 hour.]

Assay preparation— Remove, as completely as possible, the contents of not fewer than 20 Capsules, and weigh. Transfer an accurately weighed portion of the mixed powder, equivalent to about 10 mg of phenoxybenzamine hydrochloride, to a 50-mL volumetric flask. Add about 40 mL of acetonitrile, and sonicate for 15 minutes with occasional swirling. Cool, and dilute with acetonitrile to volume to obtain a solution having a phenoxybenzamine hydrochloride concentration of 0.2 mg per mL, based on the label claim. Allow the sample to stand undisturbed for 30 minutes such that the undissolved material settles to the bottom. Transfer the top clear solution into HPLC vials, and use as the Assay preparation.

Chromatographic system— The liquid chromatograph is equipped with a 268-nm detector and a 4.6-mm × 150-cm column that contains packing L7. The flow rate is about 1.0 mL per minute. The column is maintained at ambient temperatures. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution R, between the phenoxybenzamine hydrochloride and the unknown peak that elutes after the phenoxybenzamine peak (approximately at about 9.4 minutes) is not less than 4. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for an average of five injections determined from the phenoxybenzamine hydrochloride peak is not more than 2%.

Procedure —Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in percentage of label claim, of phenoxybenzamine hydrochloride (C18H22ClNO·HCl) in the portion of Capsules taken by the formula: in which CS is the concentration, in mg per mL, of USP Phenoxybenzamine Hydrochloride RS in the Standard preparation;CU is the concentration, in mg per mL, of phenoxybenzamine hydrochloride in the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.