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求助USP40 dalfampridine的标准，谢谢！

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MONOGRAPHS

USP

DALFAMPRIDINE

REFERENCE STANDARDS







Dalfampridine

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C5H6N294.11
4-Pyridinamine;
4-Aminopyridine[504-24-5].DEFINITION
Dalfampridine contains NLT 98.0% and NMT 102.0% of dalfampridine (C5H6N2).

IDENTIFICATION
•A. Infrared Absorption 〈197〉:
[Note—Methods described in〈197K〉 or 〈197A〉 may be used.]
•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
&#8226rocedure
Solution A:
3.03 g/L of sodium 1-heptanesulfonate, 1.36 g/L of monobasic potassium phosphate, and 1.15 g/L ofphosphoric acid in water
Solution B:
Acetonitrile
Mobile phase:
See Table 1.

Table 1

Time
(min)

Solution A
(%)

Solution B
(%)

0.0

90

10

5.0

90

10

15.0

80

20

20.0

80

20

20.1

90

10

25.0

90

10

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Diluent:
Solution A and Solution B (90:10)
System suitability stock solution:
0.04 mg/mL of USP Dalfampridine Related Compound A RS prepared as follows. Transfer a suitable quantity of USP Dalfampridine Related Compound A RS to an appropriate volumetric flask and add 20% of the total flask volume ofDiluent. Sonicate for about 5 min. Allow to cool to room temperature and dilute with Diluent to volume. Use within 24 h.
System suitability solution:
0.0002 mg/mL of USP Dalfampridine Related Compound A RS from System suitability stock solution and 0.2 mg/mL of USP Dalfampridine RS in Diluent prepared as follows. Transfer a suitable quantity of USP Dalfampridine RS to an appropriate volumetric flask, add an appropriate volume of System suitability stock solution, and add 25% of the total flask volume of Diluent. Sonicate for NLT 5 min. Allow to cool to room temperature and dilute with Diluentto volume. Pass the resulting solution through a suitable filter, discard NLT the first 2 mL, and use the filtrate.
Standard solution:
0.2 mg/mL of USP Dalfampridine RS inDiluent prepared as follows. Transfer a suitable quantity of USP Dalfampridine RS to an appropriate volumetric flask and add 25% of the total flask volume of Diluent. Sonicate for NLT 5 min. Allow to cool to room temperature and dilute with Diluent to volume. Pass the resulting solution through a suitable filter and use the filtrate.
Sample solution:
0.2 mg/mL of Dalfampridine in Diluentprepared as follows. Transfer a suitable quantity of Dalfampridine to an appropriate volumetric flask and add 25% of the total flask volume of Diluent. Sonicate for NLT 5 min. Allow to cool to room temperature and dilute withDiluent to volume. Pass the resulting solution through a suitable filter and use the filtrate.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode:
LC
Detector:
UV 275 nm
Column:
4.6-mm × 10.0-cm; 3.5-μm packing L1
Column temperature:
30°
Flow rate:
2 mL/min
Injection volume:
10 μL

System suitability
Samples:
System suitability solution and Standard solution[Note—See Table 2 for the relative retention times.]
Suitability requirements
Resolution:
NLT 2.0 between dalfampridine and dalfampridine related compound A, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Relative standard deviation:
NMT 1.0%, Standard solution


Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of dalfampridine (C5H6N2) in the portion of Dalfampridine taken:

Result = (rU/rS) × (CS/CU) × 100

rU	= peak response from the Sample solution
rS	= peak response from the Standard solution
CS	= concentration of USP Dalfampridine RS in the Standard solution (mg/mL)
CU	= concentration of Dalfampridine in the Sample solution (mg/mL)

Acceptance criteria:
98.0%–102.0%


IMPURITIES
•Residue on Ignition 〈281〉
Ignition temperature:
800°
Acceptance criteria:
NMT 0.3%

•Limit of Dalfampridine Related Compound B and Dalfampridine Related Compound C
[Note—This test should be conducted if dalfampridine related compound B and dalfampridine related compound C are possible from the manufacturing process.]
Solution A, Solution B, Mobile phase, andDiluent:
Prepare as directed in the Assay.
Standard solution:
2 μg/mL each of USP Dalfampridine Related Compound B RS and USP Dalfampridine Related Compound C RS in Diluent
Sensitivity solution:
0.1 μg/mL each of USP Dalfampridine Related Compound B RS and USP Dalfampridine Related Compound C RS from Standard solution in Diluent
Sample solution:
2000 μg/mL of Dalfampridine in Diluentprepared as follows. Transfer a suitable quantity of Dalfampridine to an appropriate volumetric flask and add 25% of the total flask volume of Diluent. Sonicate for NLT 5 min. Allow to cool to room temperature and dilute withDiluent to volume.
Chromatographic system:
Proceed as directed in theAssay, except use an Injection volume of 30 μL.
System suitability
Samples:
Standard solution and Sensitivity solution[Note—See Table 2 for the relative retention times.]
Suitability requirements
Relative standard deviation:
NMT 10% each for dalfampridine related compound B and dalfampridine related compound C, Standard solution
Signal-to-noise ratio:
NLT 10 each for dalfampridine related compound B and dalfampridine related compound C, Sensitivity solution


Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of dalfampridine related compound B and dalfampridine related compound C in the portion of Dalfampridine taken:

Result = (rU/rS) × (CS/CU) × 100

rU	= peak response of dalfampridine related compound B or dalfampridine related compound C from the Sample solution
rS	= peak response of dalfampridine related compound B or dalfampridine related compound C from the Standard solution
CS	= concentration of USP Dalfampridine Related Compound B RS or USP Dalfampridine Related Compound C RS in the Standard solution (μg/mL)
CU	= concentration of Dalfampridine in the Sample solution (μg/mL)

Acceptance criteria:
NMT 0.0075% each for dalfampridine related compound B and dalfampridine related compound C

•Organic Impurities
Solution A, Solution B, Mobile phase, Diluent, and System suitability solution:
Prepare as directed in the Assay.
Standard solution:
2 μg/mL of USP Dalfampridine RS inDiluent
Sensitivity solution:
0.1 μg/mL of USP Dalfampridine RSfrom Standard solution in Diluent
Sample solution:
200 μg/mL of Dalfampridine in Diluentprepared as follows. Transfer a suitable quantity of Dalfampridine to an appropriate volumetric flask and add 25% of the total flask volume of Diluent. Sonicate for NLT 5 min. Allow to cool to room temperature and dilute withDiluent to volume. Pass the resulting solution through a suitable filter and use the filtrate.
Chromatographic system:
Proceed as directed in theAssay, except use a Detector wavelength of 265 nm for isonicotinamide.
System suitability
Samples:
System suitability solution, Standard solution, and Sensitivity solution[Note—See Table 2 for the relative retention times.]
Suitability requirements
Resolution:
NLT 2.0 between dalfampridine and dalfampridine related compound A, System suitability solution
Tailing factor:
NMT 2.0 for dalfampridine, System suitability solution
Relative standard deviation:
NMT 5.0% for dalfampridine, Standard solution
Signal-to-noise ratio:
NLT 10, Sensitivity solution


Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of isonicotinamide in the portion of Dalfampridine taken:

Result = (rU/rS) × (CS/CU) × (1/F) × 100

rU	= peak response of isonicotinamide at 265 nm from the Sample solution
rS	= peak response of dalfampridine at 275 nm from the Standard solution
CS	= concentration of USP Dalfampridine RS in the Standard solution (μg/mL)
CU	= concentration of Dalfampridine in the Sample solution (μg/mL)
F	= relative response factor (see Table 2)

Calculate the percentage of dalfampridine related compound A and any other unspecified impurity in the portion of Dalfampridine taken:

Result = (rU/rS) × (CS/CU) × (1/F) × 100

rU	= peak response of dalfampridine related compound A or any unspecified impurity at 275 nm from the Sample solution
rS	= peak response of dalfampridine at 275 nm from the Standard solution
CS	= concentration of USP Dalfampridine RS in the Standard solution (μg/mL)
CU	= concentration of Dalfampridine in the Sample solution (μg/mL)
F	= relative response factor (see Table 2)

Acceptance criteria:
See Table 2. Disregard peaks less than 0.05%.

Table 2

Name

Relative
Retention
Time

Relative
Response
Factor

Acceptance
Criteria,
NMT (%)

Isonicotinamide

0.64

0.45

0.15

Dalfampridine

1.0

—

—

Dalfampridine
related
compound A

1.2

1.6

0.10

Dalfampridine
related
compound Ba

2.4

—

—

Dalfampridine
related
compound Ca

6.4

—

—

Any individual
unspecified
impurity

—

1.0

0.10

Total impuritiesb

—

—

0.50

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[size=0.8em]a  This impurity is quantified using the Limit of Dalfampridine Related Compound B and Dalfampridine Related Compound C test.
b  The sum of all impurities from the test for Organic Impurities and the Limit of Dalfampridine Related Compound B and Dalfampridine Related Compound C test.




SPECIFIC TESTS
•Water Determination 〈921〉, Method I, Method Ia:
NMT 0.3%

ADDITIONAL REQUIREMENTS
&#8226ackaging and Storage:
Preserve in tight containers.
•USP Reference Standards 〈11〉
USP Dalfampridine RS
USP Dalfampridine Related Compound A RS4-Aminopyridine 1-oxide.
C5H6N2O110.11
USP Dalfampridine Related Compound B RS3,5-Dibromopyridin-4-amine.
C5H4Br2N2251.91
USP Dalfampridine Related Compound C RS1,3-Di(pyridin-4-yl)urea.
C11H10N4O214.23

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Auxiliary Information-

Please [color=blue !important]check for your question in the FAQs before contacting USP.

Topic/Question

Contact

Expert Committee

DALFAMPRIDINE

[color=blue !important]Heather R. Joyce
Senior Scientific Liaison
+1 (301) 998-6792

CHM42015 Chemical Medicines Monographs 4

Page Information:

• USP41-NF36 - 1146
• USP40-NF35 1S - 8250
  

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meimei权

从网页版复制粘贴的，效果不是很好，希望能帮到你

Elijah

drug future上可以查到USP40的标准