Dexchlorpheniramine Maleate

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 

Dexchlorpheniramine Maleate, dried at 65° for 4 h, contains NLT 98.0% and NMT 102.0% of dexchlorpheniramine maleate (C₁₆H₁₉CIN₂ . C₄H₄O₄). 

2 IDENTIFICATION

Change to read:  

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

B. The retention times of the maleic acid and dexchlorpheniramine peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay. 

3 ASSAY 

3.1 Procedure 

Solution A: 5.44 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 3.0 ± 0.1. 

Solution B: Acetonitrile 

Diluent: Acetonitrile and Solution A (5:95) 

System suitability stock solution: 0.02 mg/mL each of USP Pheniramine Maleate RS, USP Chlorpheniramine Related Compound B RS, and USP Chlorpheniramine Related Compound C RS in Diluent. Sonicate for 1 min. 

System suitability solution: 0.5 mg/mL of USP Dexchlorpheniramine Maleate RS and 2 µg/mL each of USP Pheniramine Maleate RS, USP Chlorpheniramine Related Compound B RS, and USP Chlorpheniramine Related Compound C RS in Diluent, prepared as follows. Transfer 5.0 mg of USP Dexchlorpheniramine Maleate RS to a 10-mL volumetric ask, add 5 mL of Diluent and 1.0 mL of the System suitability stock solution, and dilute with Diluent to volume. Sonicate for 1 min. 

Standard solution: 0.5 mg/mL of USP Dexchlorpheniramine Maleate RS in Diluent. Sonicate for 1 min. 

Sample solution: 0.5 mg/mL of Dexchlorpheniramine Maleate in Diluent. Sonicate for 1 min. 

Mobile phase: See Table 1. 

Table 1 

Chromatographic system  

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 225 nm 

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

Column temperature: 30° 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times of maleic acid, chlorpheniramine related compound C, and dexchlorpheniramine are 0.18, 0.94, and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 1.5 between chlorpheniramine related compound C and dexchlorpheniramine; NLT 2.0 between chlorpheniramine related compound B and pheniramine, System suitability solution 

Tailing factor: NMT 2.0, Standard solution 

Relative standard deviation: NMT 0.73%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of dexchlorpheniramine maleate (C₁₆H₁₉CIN₂ . C₄H₄O₄) in the portion of Dexchlorpheniramine Maleate taken: 

Result = (r_u/r_s) x (C_s/C_u) × 100 

r_u = peak response for dexchlorpheniramine from the Sample solution 

r_s = peak response for dexchlorpheniramine from the Standard solution 

C_s = concentration of USP Dexchlorpheniramine Maleate RS in the Standard solution (mg/mL) 

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

Acceptance criteria: 98.0%–102.0%, previously dried at 65° for 4 h 

4 IMPURITIES 

4.1 Residue on Ignition 〈281〉: NMT 0.2% 

4.2 Organic Impurities 

Solution A, Solution B, Diluent, System suitability solution, Mobile phase, and Chromatographic system: Proceed as directed in the Assay. Standard solution: 2.8 µg/mL of USP Dexchlorpheniramine Maleate RS in Diluent, equivalent to 2.0 µg/mL of dexchlorpheniramine. Sonicate for 1 min. 

Sensitivity solution: 0.74 µg/mL of USP Pheniramine Maleate RS in Diluent 

Sample solution: 0.5 mg/mL of Dexchlorpheniramine Maleate in Diluent. Sonicate for 1 min. 

System suitability 

Samples: System suitability solution, Standard solution, and Sensitivity solution 

Suitability requirements 

Resolution: NLT 1.5 between chlorpheniramine related compound C and dexchlorpheniramine; NLT 2.0 between chlorpheniramine related compound B and pheniramine, System suitability solution 

Signal-to-noise ratio: NLT 10, Sensitivity 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 Dexchlorpheniramine Maleate taken: 

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

r_u = peak response of each impurity from the Sample solution 

r_s = peak response of dexchlorpheniramine from the Standard solution 

C_s = concentration of dexchlorpheniramine in the Standard solution (mg/mL) 

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

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. Disregard peaks having areas less than 0.05% of dexchlorpheniramine. 

Table 2 

a Salt counter ion is included in the table for identication purposes only.

b Di(pyridin-2-yl)amine. Used only to establish system suitability. 

c 3-(4-Chlorophenyl-N-methyl-3-(pyridin-2-yl)propan-1-amine. Used only to establish system suitability. 

4.3 Enantiomeric Purity 

System suitability solution: 0.7 mg/mL of chlorpheniramine in 2-propanol prepared as follows. Dissolve 10.0 mg of USP Chlorpheniramine Maleate RS in 3 mL of water. Make the solution basic by adding a few drops of concentrated ammonium hydroxide, and shake with 5 mL of methylene chloride. Separate the layers and evaporate the lower, methylene chloride layer on a water bath until an oily residue is obtained. Dissolve the residue, and dilute with 2-propanol to 10.0 mL. 

Standard stock solution: 0.7 mg/mL of dexchlorpheniramine in 2-propanol prepared as follows. Dissolve 10.0 mg of USP Dexchlorpheniramine Maleate RS in 3 mL of water. Make the solution basic by adding a few drops of concentrated ammonium hydroxide, and shake with 5 mL of methylene chloride. Separate the layers and evaporate the lower, methylene chloride layer on a water bath until an oily residue is obtained. Dissolve the residue, and dilute with 2-propanol to 10.0 mL. 

Standard solution: 0.014 mg/mL of dexchlorpheniramine in 2-propanol from the Standard stock solution 

Sample solution: 0.7 mg/mL of dexchlorpheniramine in 2-propanol prepared as follows. Dissolve 10.0 mg of Dexchlorpheniramine Maleate in 3 mL of water. Make the solution basic by adding a few drops of concentrated ammonium hydroxide, and shake with 5 mL of methylene chloride. Separate the layers and evaporate the lower, methylene chloride layer on a water bath until an oily residue is obtained. Dissolve the residue, and dilute with 2-propanol to 10.0 mL. 

Mobile phase: n-Hexane, 2-propanol, and diethylamine (980:20:3) 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; 10-µm packing L51 

Flow rate: 1 mL/min 

Injection volume: 10 µL 

System suitability 

[Note—Under these conditions the dexchlorpheniramine (S-enantiomer) elutes rst.] 

Sample: System suitability solution 

Suitability requirements 

Resolution: NLT 1.5 between the R-enantiomer and dexchlorpheniramine (S-enantiomer) 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the R-enantiomer in the portion of dexchlorpheniramine taken: 

Result = (r_u/r_s) x (C_s/C_u) × 100 

r_u = peak response of the R-enantiomer from the Sample solution 

r_s = peak response of dexchlorpheniramine from the Standard solution 

C_s = concentration of dexchlorpheniramine in the Standard solution (mg/mL) 

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

Acceptance criteria: NMT 2% 

5 SPECIFIC TESTS 

5.1 Optical Rotation, Specific Rotation〈781S〉 

Sample solution: 50 mg/mL, in dimethylformamide 

Acceptance criteria: +39.5° to +43.0° 

5.2 pH 〈791〉 

Sample solution: 10 mg/mL 

Acceptance criteria: 4.0–5.0 

6 ADDITIONAL REQUIREMENTS 

6.1 Loss on Drying 〈731〉 

Analysis: Dry a sample at 65° for 4 h. 

Acceptance criteria: NMT 0.5% 

6.2 Packaging and Storage: Preserve in tight, light-resistant containers. 

6.3 USP Reference Standards 〈11〉 

USP Chlorpheniramine Maleate RS 

USP Chlorpheniramine Related Compound B RS 

Di(pyridin-2-yl)amine. 

C₁₀H₉N₃           171.20 

USP Chlorpheniramine Related Compound C RS 

3-(4-Chlorophenyl-N-methyl-3-(pyridin-2-yl)propan-1-amine maleate. 

C₁₅H₁₇CIN₂ . C₄H₄O₄            376.83 

USP Dexchlorpheniramine Maleate RS 

USP Pheniramine Maleate RS