Add the following:

Change to read:

A: Infrared Absorption 197K— (for bilayer tablets)

B: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.

C: Thin-Layer Chromatographic Identification Test 201 4

Change to read:

test 1—3

test 2— If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.

Change to read:

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

Standard solution— Use the Standard preparation, prepared as directed in the Assay.

Reference solution— Use the Assay preparation.

Test solution— Use the Assay stock preparation, prepared as directed in the Assay.

Chromatographic system (see Chromatography 621)— Chromatograph the System suitability preparation as directed for Procedure: the relative retention times are about 1.2 for ephedrone and 1.0 for pseudoephedrine; the resolution, R, between pseudoephedrine and ephedrone is not less than 1.7; and the relative standard deviation for replicate injections is not more than 1.0% based on the pseudoephedrine peak. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.2 for fexofenadine related compound A, 3.1 for decarboxylated degradant, and 1.0 for fexofenadine; the resolution, R, between fexofenadine and fexofenadine related compound A is not less than 2.0; and the relative standard deviation for replicate injections is not more than 1.0% based on the fexofenadine peak and not more than 3.0% based on the individual peaks for fexofenadine related compound A and decarboxylated degradant.

Procedure— Separately inject equal volumes (about 20 µL) of the Test solution and the Reference solution into the chromatograph, record the chromatograms, and measure all of the peak responses. Calculate the percentage of fexofenadine related compound A and decarboxylated degradant in the portion of Tablets taken by the formula: in which CS is the concentration, in mg per mL, of either USP Fexofenadine Related Compound A RS or decarboxylated degradant in the Standard solution; CT is the nominal concentration, in mg per mL, of fexofenadine hydrochloride4 in the Test solution; ri is the individual peak area of either fexofenadine related compound A or decarboxylated degradant obtained from the Test solution; and rS is the peak area of fexofenadine related compound A obtained from the Standard solution. Calculate the percentage of ephedrone in the portion of Tablets taken by the formula: in which F is the relative response factor for ephedrone (F is 0.394); CS is the concentration, in mg per mL, of USP Pseudoephedrine Hydrochloride RS in the Standard solution; CT is the nominal concentration, in mg per mL, of pseudoephedrine hydrochloride4 in the Test solution; ri is the peak height for ephedrone obtained from the Test solution; and rS is the peak height for pseudoephedrine obtained from the Standard solution. Calculate the percentage of any other impurities in the portion of Tablets taken by the formula: in which ri is the individual peak area response for an individual unknown impurity in the Test solution; 25 is the difference in concentration between the Test solution and the Reference solution; rS is the peak area response for fexofenadine hydrochloride4 obtained from the Reference solution; and rT is the sum of the peak area responses of all unknown impurities in the Test solution. Disregard any peak below 0.05%.

Change to read:

Buffer solution— Dissolve 6.8 g of sodium acetate and 16.22 g of sodium 1-octanesulfonate in water, and dilute with water to 1 L. Adjust with glacial acetic acid to a pH of 4.6.

Mobile phase— Prepare a filtered and degassed mixture of methanol and Buffer solution (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).

System suitability preparation— Transfer an accurately weighed quantity, about 40 mg, of USP Pseudoephedrine Hydrochloride RS to a 50-mL volumetric flask. Add 5 mL of tert-butylhydroperoxide solution, and sonicate. Cover the flask opening with aluminum foil, and place the flask in an oven at about 90 for 60 minutes. Remove from the oven, and allow to cool. Add 35 mL of Mobile phase, and cool to room temperature. Dilute with Mobile phase to volume, and mix. The degradation of pseudoephedrine hydrochloride by this process produces the related compound ephedrone.

Related compounds preparation— Dissolve accurately weighed quantities of USP Fexofenadine Related Compound A RS and decarboxylated degradant*4 in a volume of methanol, and dilute quantitatively, and stepwise if necessary, with Buffer solution to maintain a ratio of methanol and Buffer solution (60:40). Dilute quantitatively, and stepwise if necessary, with methanol and Buffer solution (60:40) to obtain a solution having known concentrations of 0.2 mg per mL for each component. Dilute 10.0 mL of this solution with Mobile phase to 100 mL to obtain a final solution having known concentrations of 0.02 mg per mL for each component.

Standard stock preparation— Dissolve accurately weighed quantities of USP Fexofenadine Hydrochloride RS and USP Pseudoephedrine Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having known concentrations of about 0.4 mg per mL and 0.8 mg per mL of fexofenadine hydrochloride4 and pseudoephedrine hydrochloride,4 respectively.

Standard preparation— Dilute 6.0 mL of the Standard stock preparation and 15.0 mL of the Related compounds preparation with Mobile phase to 50 mL to obtain a solution having known concentrations of about 0.048 mg of fexofenadine hydrochloride per mL, 0.096 mg of pseudoephedrine hydrochloride per mL, 0.006 mg of fexofenadine related compound A per mL, and 0.006 mg of decarboxylated degradant per mL.

Assay stock preparation— Transfer not fewer than 10 whole Tablets to a 500-mL volumetric flask. Add 300 mL of methanol, and shake by mechanical means at high speed for 60 minutes. Sonicate the flask for 60 minutes at 40. Add 150 mL of Buffer solution, and sonicate for 60 minutes at 40. Vent the flask, and vigorously shake the flask by hand at 15-minute intervals during the mechanical shaking and sonication steps. Cool to room temperature, and dilute with Buffer solution to volume to obtain a solution containing approximately 1.2 mg of fexofenadine hydrochloride4 per mL and 2.4 mg of pseudoephedrine hydrochloride4 per mL. Pass a portion of this solution through a filter having a 0.45-µm or finer porosity, and use the filtrate.

Assay preparation— Dilute 4.0 mL of the Assay stock preparation filtrate with Mobile phase to 100 mL. The final concentrations of fexofenadine hydrochloride4 and pseudoephedrine hydrochloride4 are 0.048 mg per mL and 0.096 mg per mL, respectively.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 5-cm column that contains 5-µm packing L6 connected in series to a 4.6-mm × 25-cm column that contains 5-µm packing L11. The flow rate is about 1.5 mL per minute. The column temperature is maintained at 35. Chromatograph the System suitability preparation as directed for Procedure: the relative retention times are about 1.2 for ephedrone and 1.0 for pseudoephedrine; the resolution, R, between pseudoephedrine and ephedrone is not less than 1.7; and the relative standard deviation for replicate injections is not more than 1.0% based on the pseudoephedrine peak. Chromatograph the Standard preparation,4 and record the peak responses as directed for Procedure: the relative retention times are about 1.2 for fexofenadine related compound A, 3.1 for decarboxylated degradant, and 1.0 for fexofenadine; the resolution, R, between fexofenadine and fexofenadine related compound A is not less than 2.0; and the relative standard deviation for replicate injections is not more than 1.0% based on the fexofenadine peak.

Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the fexofenadine and pseudoephedrine peaks. Calculate the percentage of the label claim of fexofenadine hydrochloride (C32H39NO4·HCl) and pseudoephedrine hydrochloride (C10H15NO·HCl) in the portion of Tablets taken by the formula: in which CS is the concentration, in mg per mL, of either USP Fexofenadine Hydrochloride RS or USP Pseudoephedrine Hydrochloride RS in the Standard preparation; CT is the nominal concentration, in mg per mL, of either fexofenadine hydrochloride4 or pseudoephedrine hydrochloride4 in the Assay preparation; and rU and rS are the peak responses obtained for either fexofenadine or pseudoephedrine from the Assay preparation and the Standard preparation, respectively.