Mobile phase and Diluent— Prepare as directed in the Assay.

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

Standard solution— Pipet 5.0 mL of Standard stock solution into a 100-mL volumetric flask, dilute with Diluent to volume, and mix. 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 column temperature is maintained between 25 and 35. 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 area 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 the peak areas in the Test solution and the area of the main peak in the Standard solution. Calculate the percentage of each impurity in the portion of Loratadine taken by the formula: in which C is the concentration, in mg per mL, of USP Loratadine RS in the Standard solution; F is the relative response factor for each impurity, if known (F is 0.25 for 4-(8-chloro-11-fluoro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)-1-piperidinecarboxylate ethyl); ri is the peak area response for each impurity in the Test solution; rS is the peak area response of loratadine in the Standard solution; and W is the quantity, in mg, of Loratadine taken to prepare the Test 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 not more than 0.3% of total impurities is found.

Solution A— Dissolve 0.96 g of 1-pentanesulfonic acid sodium salt in 900 mL of water. Adjust with phosphoric acid solution (1 in 10) to a pH of 3.00 ± 0.05, dilute with water to 1 L, filter, and degas.

Solution B— Use acetonitrile.

Mobile phase— Use variable mixtures of Solution A and Solution B as directed for Chromatographic system. Make adjustments if necessary (see System Suitability under Chromatography 621).

Standard solution— Dissolve accurately weighed quantities of USP Loratadine RS, USP Loratadine Related Compound A RS, and USP Loratadine Related Compound B RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution containing about 0.1 mg of each compound per mL. Transfer 1.0 mL of this solution to a 10-mL volumetric flask, add 2 mL of Solution A, dilute with methanol to volume, and mix to obtain a solution having a known concentration of about 0.01 mg of each per mL.

Test solution— Transfer about 100 mg of Loratadine, accurately weighed, to a 10-mL volumetric flask, and dissolve in 2 mL of methanol. Add 2 mL of Solution A, then dilute with methanol to volume, and mix.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column containing 5-µm packing L1. The flow rate is about 1.2 mL per minute. The chromatograph is programmed as follows. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative retention times and response factors are as follows in the table below. The resolution, R, between loratadine related compound A and loratadine related compound B is not less than 1.5; and the relative standard deviation of the loratadine peak response from replicate injections is not more than 10%.

Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak responses. Calculate the percentage of each impurity in the portion of Loratadine taken by the formula: in which CS is the concentration, in mg per mL, of USP Loratadine RS in the Standard solution; CT is the concentration, in mg per mL of the Test solution; F is the relative response factor as indicated in the table (F = 1.0 for unknown impurities); ri is the peak area response for the individual impurity in the Test solution; and rS is the peak response for loratadine in the Standard solution: not more than 0.1% of loratadine related compound A is found; not more than 0.1% of loratadine related compound B is found; less than 0.1% for each individual unknown impurity is found; and not more than 0.3% of total impurities is found.

100C(rU / rS)