A: Transfer about 85 mg (equivalent to about 50 mg of hydroxyzine hydrochloride) to a separator containing 25 mL of 1 N sodium hydroxide, and extract with three 20-mL portions of chloroform. Evaporate the combined chloroform extracts on a steam bath with the aid of a current of air to dryness, and dissolve the residue in 0.1 N hydrochloric acid to make 100 mL. Dilute a 1-mL portion of this solution with 0.1 N hydrochloric acid to 50 mL: the UV absorption spectrum of the solution so obtained exhibits maxima and minima at the same wavelengths as that of a 1 in 100,000 solution of USP Hydroxyzine Hydrochloride RS in 0.1 N hydrochloric acid, concomitantly measured.

B: Prepare a solution of it in a mixture of equal volumes of 0.1 N sodium hydroxide and acetone containing 2 mg per mL. Apply 10 µL of this solution and 10 µL of a solution of USP Hydroxyzine Pamoate RS in the same medium, having a concentration of 2 mg per mL to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.50-mm layer of chromatographic silica gel. Allow the spots to dry, and develop the chromatogram in 0.1 N hydrochloric acid until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and locate the spots on the plate by viewing under long-wavelength UV light: the RF value of the principal spot, representing the pamoate moiety, obtained from the test solution corresponds to that obtained from the Standard solution. Spray the plate lightly with potassium iodoplatinate TS: the RF value of the principal spot, representing the hydroxyzine moiety, obtained from the test solution corresponds to that obtained from the Standard solution.

Solvent— Use dimethyl sulfoxide.

2500C(rU / rS),

(Official January 1, 2007)

Mobile phase— Dissolve 8.65 g of sodium 1-octanesulfonate in about 1000 mL of water in a 2000-mL volumetric flask, add 4.0 mL of phosphoric acid, dilute with water to volume, mix, and filter through a membrane filter of 0.5 µm or finer porosity. Prepare a suitable mixture of this solution and acetonitrile (45:55), making any adjustments if necessary (see System Suitability under Chromatography 621).

Standard preparation— Dissolve an accurately weighed quantity of USP Hydroxyzine Hydrochloride RS in dimethylformamide to obtain a solution having a known concentration of about 1 mg per mL. Transfer 2.0 mL of the resulting solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, mix, and filter through a membrane filter of 0.5 µm or finer porosity.

Assay preparation— Transfer about 90 mg of Hydroxyzine Pamoate, accurately weighed, to a 50-mL volumetric flask, dissolve in dimethylformamide, dilute with dimethylformamide to volume, and mix. Transfer 2.0 mL of the resulting solution to a 100-mL volumetric flask, dilute with Mobile phase to volume, mix, and filter through a membrane filter of 0.5 µm or finer porosity, discarding the first 5 mL of the filtrate.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 230-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed under Procedure: the column efficiency, calculated from the analyte peak, is not less than 2000 theoretical plates, and the relative standard deviation for replicate injections is not more than 2%. Chromatograph the Assay preparation, and record the peak responses as directed under Procedure: the resolution, R, between hydroxyzine and pamoic acid is not less than 1.5.

Procedure— Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.5 for hydroxyzine and 1.0 for pamoic acid. Calculate the quantity, in mg, of C21H27ClN2O2·C23H16O6 in the portion of Hydroxyzine Pamoate taken by the formula: in which 763.27 and 447.83 are the molecular weights of hydroxyzine pamoate and hydroxyzine hydrochloride, respectively; C is the concentration, in mg per mL, of USP Hydroxyzine Hydrochloride RS in the Standard preparation; and rU and rS are the hydroxyzine peak responses obtained from the Assay preparation and the Standard preparation, respectively.