Desloratadine

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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C₁₉H₁₉ClN₂  310.82

Benzo[5,6]cyclohepta[1,2-b]pyridine, 8-chloro-6,11-dihydro-11-(4-piperidinylidene)-, 5H-;

8-Chloro-6,11-dihydro-11-(piperidin-4-ylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine  CAS RN®: 100643-71-8; UNII: FVF865388R.

1 DEFINITION

Desloratadine contains NLT 98.0% and NMT 102.0% of desloratadine (C₁₉H₁₉ClN₂), calculated on the anhydrous and solvent-free basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

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

3.1 Procedure

Buffer: Dissolve 0.865 g of sodium dodecyl sulfate in water, add 0.5 mL of trifluoroacetic acid, and dilute with water to 1 L.

Mobile phase: Acetonitrile and Buffer (43:57)

System suitability solution: 0.08 mg/mL of USP Desloratadine RS and 0.2 µg/mL of USP Desloratadine Related Compound B RS in Mobile phase

Standard solution: 0.08 mg/mL of USP Desloratadine RS in Mobile phase

Sample solution: 0.08 mg/mL of Desloratadine in Mobile phase

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 280 nm
• Column: 4.6-mm × 25-cm; 4-µm packing L1
• Column temperature: 35°
• Flow rate: 1 mL/min
• Injection volume: 100 µL
• Run time: NLT 2 times the retention time of desloratadine

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 2.0 between desloratadine related compound B and desloratadine, System suitability solution
• Tailing factor: NMT 1.5, Standard solution
• Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of desloratadine (C₁₉H₁₉ClN₂) in the portion of Desloratadine 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 Desloratadine RS in the Standard solution (mg/mL)

C_u = concentration of Desloratadine in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous and solvent-free basis.

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.2%

4.2 Organic Impurities, Procedure 1

Use Organic Impurities, Procedure 1, when the impurity profile includes desloratadine related compound B or fluorodesloratadine.

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

Standard solution: 0.08 µg/mL of USP Desloratadine RS in Mobile phase

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 2.0 between desloratadine related compound B and desloratadine, System suitability solution
• Tailing factor: NMT 1.5, Standard solution
• Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of desloratadine from the Standard solution 

C_s = concentration of USP Desloratadine RS in the Standard solution (µg/mL)

C_u = concentration of Desloratadine in the Sample solution (µg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1. Reporting threshold = 0.05%.

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

4.3 Organic Impurities, Procedure 2

Use Organic Impurities, Procedure 2, when the impurity profile includes dechloro desloratadine, desloratadine related compound A, or dehydrodesloratadine.

Buffer: 1.36 g/L of monobasic potassium phosphate in water. Add 10 mL of triethylamine per L of the solution, and adjust with dilute phosphoric acid (1 in 10) to a pH of 2.0.

Solution A: Acetonitrile, methanol, and Buffer (10:10:80)

Solution B: Acetonitrile, tetrahydrofuran, and Buffer (70:5:30)

Mobile phase: See Table 2.

System suitability solution: 0.15 µg/mL of USP Desloratadine Related Compound A RS and 100 µg/mL of USP Desloratadine RS in Solution A

Standard solution: 0.5 µg/mL of USP Desloratadine RS in Solution A

Sample solution: 500 µg/mL of Desloratadine in Solution A

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detector: UV 280 nm
• Column: 4.6-mm x 25-cm; 5-µm packing L7
• Flow rate: 1 mL/min
• Injection volume: 60 µL

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 3.0 between desloratadine and desloratadine related compound A, System suitability solution
• Tailing factor: NMT 3.0 for desloratadine, System suitability solution
• Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of desloratadine from the Standard solution

C_s = concentration of USP Desloratadine RS in the Standard solution (µg/mL)

C_u = concentration of Desloratadine in the Sample solution (µg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3.

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

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

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

5 SPECIFIC TESTS

Water Determination, Method I c 〈921〉: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

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

USP Reference Standards 〈11〉

USP Desloratadine RS

USP Desloratadine Related Compound A RS

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

C₁₉H₁₉BrN₂ 355.27

USP Desloratadine Related Compound B RS

8-Chloro-11-(1,2,3,6-tetrahydropyridin-4-yl)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine hydrochloride.

C₁₉H₂₀Cl₂N₂ 347.28