Loratadine

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Loratadine contains NLT 98.5% and NMT 101.0% of loratadine (C₂₂H₂₃ClN₂O₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer A (0.01 M dibasic potassium phosphate): 1.74 g/L of anhydrous dibasic potassium phosphate in water

Buffer B (0.6 M dibasic potassium phosphate): 105 g/L of anhydrous dibasic potassium phosphate in water 0.05 N hydrochloric acid: Transfer 500 mL of water to a 1000-mL volumetric flask, add 83 mL of hydrochloric acid, and dilute with water to volume. Transfer 50 mL of this solution into a 1000-mL volumetric flask, and dilute with water to volume.

Mobile phase: Acetonitrile, methanol, and Buffer A (60:60:70). Adjust with 10% phosphoric acid to an apparent pH of 7.2.

Diluent: Transfer 400 mL of 0.05 N hydrochloric acid and 80 mL of Buffer B to a 1-L volumetric flask. Dilute with a mixture of acetonitrile and methanol (1:1) to volume.

Standard solution: 0.4 mg/mL of USP Loratadine RS in Diluent

Sample solution: 0.4 mg/mL of Loratadine in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Column temperature: 25°–35°

Flow rate: 1 mL/min

Injection volume: 15 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of loratadine (C₂₂H₂₃ClN₂O₂) in the portion of Loratadine taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S= concentration of USP Loratadine RS in the Standard solution (mg/mL)

C_U = concentration of the Sample solution (mg/mL)

Acceptance criteria: 98.5%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities, Procedure 1

[Note—On the basis of the synthetic route, perform either Procedure 1 or Procedure 2. Procedure 2 is recommended if 4,8-dichloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one is a potential related compound.]

Mobile phase and Diluent: Proceed as directed in the Assay.

Standard solution: 0.8 μg/mL of USP Loratadine RS in Diluent

Sample solution: 0.4 mg/mL of Loratadine in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Column temperature: 25°–35°

Flow rate: 1 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 4.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Loratadine taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak area of each impurity from the Sample solution

r_S = peak area of loratadine from the Standard solution

C_S = concentration of USP Loratadine RS in the Standard solution (mg/mL)

C_U = concentration of Loratadine in the Sample solution (mg/mL)

F = relative response factor as listed in Table 1

Acceptance criteria: See Table 1.

Table 1

^a Ethyl 4-(8-chloro-11-fluoro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl) piperidin-1-carboxylate.

Organic Impurities, Procedure 2

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, and dilute with water to 1 L.

Solution B: Acetonitrile

Mobile phase: See Table 2.

Table 2

Standard stock solution: 0.1 mg/mL each of USP Loratadine RS, USP Loratadine Related Compound A RS, and USP Loratadine Related Compound B RS in methanol

Standard solution: 0.01 mg/mL each of USP Loratadine RS, USP Loratadine Related Compound A RS, and USP Loratadine Related Compound B RS prepared as follows. Transfer 1.0 mL of the Standard stock solution to a 10-mL volumetric flask, add 2 mL of Solution A, and dilute with methanol to volume.

Sample solution: 10 mg/mL of Loratadine prepared as follows. Transfer 100 mg of Loratadine to a 10-mL volumetric flask, and dissolve in 2mL of methanol. Add 2 mL of Solution A, and then dilute with methanol to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 25-cm; 5-μm packing L1

Flow rate: 1.2 mL/min

Injection volume: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.5 between loratadine related compound A and loratadine related compound B

Relative standard deviation: NMT 10% for the loratadine peak

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Loratadine taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak area of each individual impurity from the Sample solution

r_S = peak area of loratadine from the Standard solution

C_S = concentration of USP Loratadine RS in the Standard solution (mg/mL)

C_U = concentration of Loratadine in the Sample solution (mg/mL)

F = relative response factor as listed in Table 3

Acceptance criteria: See Table 3.

Table 3

^a 8-Chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one.

^b 8-Chloro-5,6-dihydro-11-hydroxy-11-(1-methylpiperidin-4-yl)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine.

^c 4,8-Dichloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one.

^d Ethyl 4-(8-chloro-11-hydroxy-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl) piperidin-1-carboxylate.

^e Ethyl 4-(4,8-dichloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)piperidin-1-carboxylate.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry a sample at 100° to constant weight.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store between 2° and 30°.

Labeling: If a test for Organic Impurities other than Procedure 1 is used, then the labeling states with which Organic Impurities test the article complies.

USP Reference Standards 〈11〉

USP Loratadine RS

USP Loratadine Related Compound A RS

8-Chloro-5,6-dihydro-11-(piperidin-4-ylidene)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine.

C₁₉H₁₉ClN₂ 310.82

USP Loratadine Related Compound B RS

8-Chloro-5,6-dihydro-11-(N-methylpiperidin-4-ylidene)-11H-benzo[5,6]cyclohepta[1,2-b]pyridine.

C₂₀H₂₁ClN₂ 324.85