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Dexchlorpheniramine Maleate

관리자 | 2015.08.14 16:11 | 조회 8500

L51

Amylose tris-3,5-dimethylphenylcarbamate-coated, porous, spherical, silica partilces, 5 to 10 µm in diameter.

Chiralpak AD
Chiralpak AD-H






Dexchlorpheniramine Maleate
(dex'' klor fen ir' a meen mal' ee ate).
Click to View USP ImageClick to View 3D Image

C16H19ClN2·C4H4O4
390.86 
2-Pyridinepropanamine, -(4-chlorophenyl)-N,N-dimethyl-, (S)-, (Z)-2-butenedioate (1:1);    
 
(+)-2-[p-Chloro--[2-(dimethylamino)ethyl]benzyl]pyridine maleate (1:1)    
[2438-32-6].
DEFINITION
Dexchlorpheniramine Maleate, dried at 65 for 4 h, contains NLT 98.0% and NMT 102.0% of dexchlorpheniramine maleate (C16H19ClN2·C4H4O4).
IDENTIFICATION
•  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.
ASSAY
•  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 flask, 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
Time
(min)
Solution A
(%)
Solution B
(%)
0955
1955
207030
307030
31955
40955
Chromatographic system 
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 (C16H19ClN2·C4H4O4) in the portion of Dexchlorpheniramine Maleate taken:
Result = (rU/rS) × (CS/CU) × 100

rU== peak response fordexchlorpheniramine from the Sample solution
rS== peak response fordexchlorpheniramine from theStandard solution
CS== concentration of USPDexchlorpheniramine Maleate RS in the Standard solution (mg/mL)
CU== concentration of DexchlorpheniramineMaleate in the Sample solution(mg/mL)
Acceptance criteria: 98.0%–102.0%, previously dried at 65 for 4 h
IMPURITIES
•  Residue on Ignition 281: NMT 0.2%
Change to read:
•  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,(ERR 1-Oct-2014) 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 = (rU/rS) × (CS/CU) × (1/F) × 100

rU== peak response of each impurity from theSample solution
rS== peak response ofdexchlorpheniramine from theStandard solution
CS== concentration of dexchlorpheniraminein the Standard solution (mg/mL)
CU== concentration of DexchlorpheniramineMaleate 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
NameRelative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
Maleic acida0.18
Chlorpheniramine 
related compound Bb
0.49
Pheniramine0.570.400.4
Chlorpheniramine 
related compound Cc
0.97
Dexchlorpheniramine1.0
Any other unspecified impurity1.00.10
Total impurities1
a  Salt counter ion is included in the table for identification 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.
•  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 
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 first. ]
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 = (rU/rS) × (CS/CU) × 100

rU== peak response of the R-enantiomer from the Sample solution
rS== peak response ofdexchlorpheniramine from theStandard solution
CS== concentration of dexchlorpheniraminein the Standard solution (mg/mL)
CU== concentration of dexchlorpheniraminein the Sample solution (mg/mL)
Acceptance criteria: NMT 2%
SPECIFIC TESTS
•  Optical Rotation, Specific Rotation781S
Sample solution: 50 mg/mL, in dimethylformamide
Acceptance criteria: +39.5 to +43.0
•  pH 791
Sample solution: 10 mg/mL
Acceptance criteria: 4.0–5.0
ADDITIONAL REQUIREMENTS
•  Loss on Drying 731
Analysis: Dry a sample at 65 for 4 h.
Acceptance criteria: NMT 0.5%
•  Packaging and Storage: Preserve in tight, light-resistant containers.
•  USP Reference Standards 11
USP Chlorpheniramine Maleate RS Click to View Structure
USP Chlorpheniramine Related Compound B RS Click to View Structure 
Di(pyridin-2-yl)amine.
 
    C10H9N3    
    171.20
USP Chlorpheniramine Related Compound C RS Click to View Structure 
3-(4-Chlorophenyl-N-methyl-3-(pyridin-2-yl)propan-1-amine.
 
    C15H17ClN2    
    260.76
USP Dexchlorpheniramine Maleate RS Click to View Structure
USP Pheniramine Maleate RS Click to View Structure
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/QuestionContactExpert Committee
MonographAlan R Potts, PhD 
Principal Scientific Liaison
(301) 816-8364
(SM42010) Monographs - Small Molecules 4
Reference StandardsRS Technical Services
1-301-816-8129
rstech@usp.org
USP38–NF33 Page 3044
Pharmacopeial Forum: Volume No. 38(6)
Chromatographic Column— 
Chromatographic columns text is not derived from, and not part of, USP 38 or NF 33.



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