Dofetilide
(doe fet' i lide).
Click to View Image

C19H27N3O5S2 441.56
Methanesulfonamide, N-[4-[2-[methyl[2-[4-[(methylsulfonyl)amino]phenoxy]ethyl]amino]ethyl]phenyl]-;     
-[(p-Methanesulfonamidophenethyl)methylamino]methanesulfono-p-phenetidide      [115256-11-6].
DEFINITION
Dofetilide contains NLT 97.0% and NMT 103.0% of C19H27N3O5S2, calculated on the anhydrous, solvent-free basis.
IDENTIFICATION
•  B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
•  Procedure
Potassium hydroxide solution:  0.56 g/mL of potassium hydroxide
Buffer:  1.36 g of monobasic potassium phosphate and 5 mg of ascorbic acid in 1 L of water. Adjust with Potassium hydroxide solution to a pH of 7.0.
Mobile phase:  Acetonitrile and Buffer (1:3)
System suitability solution:  25 µg/mL of USP Dofetilide RS and 0.5 µg/mL of USP Dofetilide Related Compound A RS in Mobile phase
Standard solution:  25 µg/mL of USP Dofetilide RS in Mobile phase
Sample solution:  25 µg/mL of Dofetilide in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 230 nm
Column:  3.9-mm × 15-cm; 4-µm packing L7
Temperature:  30
Flow rate:  1 mL/min
Injection size:  50 µL
System suitability 
Samples:  System suitability solution and Standard solution
Suitability requirements 
Resolution:  NLT 8.0 between dofetilide and dofetilide related compound A, System suitability solution
Relative standard deviation:  NMT 2.0%, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C19H27N3O5S2 in the portion of Dofetilide taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of dofetilide from the Sample solution
rS== peak response of dofetilide from the Standard solution
CS== concentration of dofetilide in the Standard solution (µg/mL)
CU== concentration of Dofetilide in the Sample solution (µg/mL)
Acceptance criteria:  97.0%–103.0% on the anhydrous and solvent-free basis
IMPURITIES
Inorganic Impurities 
•   Residue on Ignition 281: NMT 0.1%
•   Heavy Metals, Method II 231: NMT 20 ppm
Organic Impurities 
•  Procedure
Buffer:  0.78 g/L of ammonium acetate. Adjust with glacial acetic acid to a pH of 5.0 ± 0.1.
Diluent:  Acetonitrile and Buffer (3:22)
Solution A:  Buffer
Solution B:  Methanol
Mobile phase:  See the gradient table below.
Time
(min)
Solution A
(%)
Solution B
(%)
0 88 12
5 88 12
25 70 30
30 70 30
System suitability solution:  1.25 µg/mL each of USP Dofetilide RS and USP Dofetilide Related Compound A RS in Diluent
Standard solution:  1.25 µg/mL of USP Dofetilide RS in Diluent
Diluted standard solution:  0.125 µg/mL of USP Dofetilide RS in Diluent from the Standard solution
Sample solution:  0.25 mg/mL of Dofetilide in Diluent
Chromatographic system  
Mode:  LC
Detector:  UV 230 nm
Column:  3.9-mm × 15-cm; 5-µm packing L1
Temperature:  30
Flow rate:  1 mL/min
Injection size:  50 µL
System suitability 
Samples:  System suitability solution and Diluted standard solution
System suitability requirements 
Resolution:  NLT 5.0 between dofetilide and dofetilide related compound A, System suitability solution
Column efficiency:  NLT 35,000 theoretical plates for the dofetilide peak, System suitability solution
Tailing factor:  NMT 1.5 for the dofetilide peak, System suitability solution
Relative standard deviation:  NMT 10.0%, Diluted standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Dofetilide taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU== peak response for each impurity from the Sample solution
rS== peak response of dofetilide from the Standard solution
CS== concentration of USP Dofetilide RS in the Standard solution (mg/mL)
CU== concentration of Dofetilide in the Sample solution (mg/mL)
F== relative response factor (see Impurity Table 1)
Acceptance criteria 
Individual impurities:  See Impurity Table 1.
Total impurities:  See Impurity Table 1.
Impurity Table 1
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance Criteria,
NMT (%)
Dofetilide related compound Aa 0.9 1.04 0.5
Dofetilide 1.0
Any other individual
unspecified impurity
1.00b 0.1
Total impurities 0.5
a   N-[4-(2-(2-[4-(Methanesulfonamido)phenoxy]ethylamino)ethyl)phenyl]
methanesulfonamide.
b   Unless otherwise determined.
SPECIFIC TESTS
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.
•  USP Reference Standards 11
USP Dofetilide RS Click to View Structure
USP Dofetilide Related Compound A RS Click to View Structure
N-[4-(2-{2-[4-(Methanesulfonamido)phenoxy]ethylamino}ethyl)phenyl]methanesulfonamide.    427.54
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Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
1-301-816-8349
(SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 2962
Pharmacopeial Forum: Volume No. 35(5) Page 1135