Dofetilide
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].
(doe fet' i lide).
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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
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
• Water Determination, Method I 
921
:
NMT 1.0%
921:
NMT 1.0%
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
• USP Reference Standards 11
11
USP Dofetilide RS 
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USP Dofetilide Related Compound A RS
N-[4-(2-{2-[4-(Methanesulfonamido)phenoxy]ethylamino}ethyl)phenyl]methanesulfonamide. 427.54
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N-[4-(2-{2-[4-(Methanesulfonamido)phenoxy]ethylamino}ethyl)phenyl]methanesulfonamide. 427.54
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| 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