A: Thin-Layer Chromatographic Identification Test 201—

B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Medium: 0.1 N hydrochloric acid; 900 mL.

Apparatus 2: 50 rpm.

Time: 60 minutes.

Procedure— Determine the amount of C22H23ClN2O2 dissolved from UV absorption at the wavelength of maximum absorbance at about 280 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 Loratadine RS in the same Medium.

Tolerances— Not less than 80% (Q) of the labeled amount of C22H23ClN2O2 is dissolved in 60 minutes.

0.01 M Dibasic potassium phosphate, 0.6 M Dibasic potassium phosphate, Mobile phase, 0.05 N Hydrochloric acid, and Diluent— Proceed as directed in the Assay under Loratadine.

Standard stock solution— Prepare as directed for Standard preparation in the Assay under Loratadine.

Standard solution— Pipet 5.0 mL of the Standard stock solution into a 100-mL volumetric flask, and dilute with Diluent to volume. Dilute quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 0.8 µg per mL.

Test solution— Use the Assay preparation.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1 mL per minute. Chromatograph the Test solution, and record the peak areas as directed for Procedure: the relative retention times are about 0.79 for 4-(8-chloro-11-fluoro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate ethyl and 1.0 for loratadine. Chromatograph the Standard solution, and record the peak areas of the main peak as directed for Procedure: the relative standard deviation for replicate injections is not more than 4.0%.

Procedure— Separately inject equal volumes (about 50 µL) of the Test solution and the Standard solution into the chromatograph, record the chromatograms, and measure all of the peak area responses in the Test solution and the peak area of the main peak in the Standard solution. Calculate the percentage of each impurity in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Loratadine RS in the Standard solution; L is the labeled quantity, in mg, of loratadine in each Tablet taken; ri is the peak area response for each impurity in the Test solution; and rS is the peak area response of loratadine in the Standard solution: not more than 0.2% of 4-(8-chloro-11-fluoro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate ethyl is found; not more than 0.1% of any other individual impurity is found; and the sum of all impurities, other than 4-(8-chloro-11-fluoro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate ethyl, is not more than 0.1%.

0.01 M Dibasic potassium phosphate, 0.6 M Dibasic potassium phosphate, Mobile phase, 0.05 N Hydrochloric acid, Diluent, and Standard preparation— Proceed as directed in the Assay under Loratadine.

Assay preparation— Transfer 10 Tablets into a 250-mL volumetric flask, add 100 mL of 0.05 N Hydrochloric acid, and shake for 40 minutes or until the Tablets are completely disintegrated. Add 75 mL of a mixture of methanol and acetonitrile (1:1), and mix. Add 20 mL of 0.6 M Dibasic potassium phosphate, and mix for 5 minutes. Dilute with a mixture of methanol and acetonitrile (1:1) to volume, and mix.

Chromatographic system (see Chromatography 621)— Prepare as directed in the Assay under Loratadine. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the capacity factor, k¢, is not less than 3.5; the tailing factor is not more than 1.7; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 15 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak response for the major peaks. Calculate the quantity, in mg, of loratadine (C22H23ClN2O2) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Loratadine RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.