Propafenone Hydrochloride Tablets
DEFINITION
Propafenone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of propafenone hydrochloride (C21H27NO3·HCl).
IDENTIFICATION
• A.
The relative retention time of the major peak from the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
• Procedure
Buffer:
0.1 M monobasic potassium phosphate prepared as follows. Dissolve 13.6 g of monobasic potassium phosphate in 900 mL of water, adjust with phosphoric acid to a pH of 3.1, and then dilute with water to 1 L.
Mobile phase:
Acetonitrile and Buffer (320:680)
Standard solution:
0.15 mg/mL of USP Propafenone Hydrochloride RS in Mobile phase
Sample stock solution:
Nominally 1.5 mg/mL of propafenone hydrochloride from NLT 20 powdered Tablets in Mobile phase, prepared as follows. Initially add Mobile phase to about 90% of the total volume, and sonicate for 10 min. Cool to room temperature, and dilute with Mobile phase to volume. Stir for 10 min, pass through a suitable filter of 0.45-µm pore size, and discard the first 5 mL of the filtrate.
Sample solution:
Nominally 0.15 mg/mL of propafenone hydrochloride in Mobile phase from Sample stock solution. Pass through a suitable filter of 0.45-µm pore size, and discard the first 5 mL of the filtrate.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 15-cm; 5-µm, packing L7
Column temperature:
45
Flow rate:
1.2 mL/min
Injection volume:
20 µL
Run time:
NLT 3 times the retention time of the propafenone peak
System suitability
Sample:
Standard solution
Suitability requirements
Tailing factor:
NMT 2.0
Relative standard deviation:
NMT 2.0%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3·HCl) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of propafenone from the Sample solution |
| rS | = | = peak response of propafenone from the Standard solution |
| CS | = | = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of propafenone hydrochloride in the Sample solution (mg/mL) |
Acceptance criteria:
90.0%–110.0%
PERFORMANCE TESTS
• Dissolution 
711
711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 2:
75 rpm
Time:
30 min
Standard solution:
0.17 mg/mL of USP Propafenone Hydrochloride RS in 0.1 N hydrochloric acid prepared as follows. To a suitable quantity of the USP Propafenone Hydrochloride RS in a suitable volumetric flask, add 0.1 N of hydrochloric acid to fill 75% of the total volume. Place the flask in a waterbath at 37 with stirring until completely dissolved. Remove the flask from the waterbath, cool to room temperature, and dilute with 0.1 N hydrochloric acid to volume.
with stirring until completely dissolved. Remove the flask from the waterbath, cool to room temperature, and dilute with 0.1 N hydrochloric acid to volume.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 5 mL of the filtrate.
Instrumental conditions
Mode:
UV
Analytical wavelength:
250 nm
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3·HCl) dissolved:
Result = (AU/AS) × (CS/L) × V × 100
| AU | = | = absorbance of propafenone from the Sample solution |
| AS | = | = absorbance of propafenone from the Standard solution |
| CS | = | = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = label claim for propafenone hydrochloride (mg/Tablet) |
| V | = | = volume of Medium, 900 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of propafenone hydrochloride is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements for Content Uniformity
905:
Meet the requirements for Content Uniformity
IMPURITIES
• Organic Impurities
Solution A:
2.61 g/L of anhydrous dipotassium hydrogen phosphate in water. Adjust with phosphoric acid to a pH of 2.5.
Solution B:
Acetonitrile
Mobile phase:
See Table 1.
Table 1
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 71 | 29 |
| 8 | 71 | 29 |
| 20 | 29 | 71 |
| 30 | 29 | 71 |
| 31 | 71 | 29 |
| 36 | 71 | 29 |
Diluent:
Solution A and Solution B (650:350)
System suitability solution:
0.1 mg/mL each of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS in Diluent
Standard solution:
1 µg/mL each of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS in Diluent
Sample solution:
Nominally 1 mg/mL of propafenone hydrochloride in Diluent, prepared from NLT 20 powdered Tablets. Initially add Diluent to about 90% of the total volume, sonicate for 10 min, and cool to room temperature. Dilute with Diluent to volume, and stir for 10 min. Pass through a suitable filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 220 nm
Column:
4.6-mm × 15-cm; 5-µm, packing L7
Column temperature:
30
Flow rate:
1 mL/min
Injection volume:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 3.0 between propafenone and propafenone related compound B, System suitability solution
Tailing factor:
NMT 2.0 for the propafenone peak, Standard solution
Relative standard deviation:
NMT 5.0% for the propafenone peak, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of propafenone related compound B in the portion of the sample taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of propafenone related compound B from the Sample solution |
| rS | = | = peak response of propafenone related compound B from the Standard solution |
| CS | = | = concentration of USP Propafenone Related Compound B RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of propafenone hydrochloride in the Sample solution (µg/mL) |
Calculate the percentage of dealkyl propafenone and any other individual degradation impurity in the portion of the sample taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response of dealkyl propafenone or any other degradation impurity from the Sample solution |
| rS | = | = peak response of propafenone from the Standard solution |
| CS | = | = concentration of USP Propafenone Hydrochloride RS in the Standard solution (µg/mL) |
| CU | = | = nominal concentration of propafenone hydrochloride in the Sample solution (µg/mL) |
Acceptance criteria:
See Table 2.
Table 2
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Dealkyl propafenonea | 0.53 | 0.1 |
| Propafenone related compound Bb | 0.78 | 0.2 |
| Propafenone | 1.00 | — |
| Any other individual degradation impurity | — | 0.2 |
| Total impuritiesc | — | 0.4 |
|
a
2¢-(2-Hydroxy-3-aminopropoxy)-3-phenylpropiophenone.
b
(2E)-1-[2-[(2RS)-2-hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylprop-2-en-1-one.
c
Total impurities include specified and unspecified impurities.
|
||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Store at controlled room temperature in tightly closed containers at a relative humidity below 60%.
• USP Reference Standards 11
11
USP Propafenone Hydrochloride RS 
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USP Propafenone Related Compound B RS
(2E)-1-[2-[(2RS)-2-Hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylprop-2-en-1-one.
C21H25NO3 339.43
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(2E)-1-[2-[(2RS)-2-Hydroxy-3-(propylamino)propoxy]phenyl]-3-phenylprop-2-en-1-one.
C21H25NO3 339.43
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D., MBA
Senior Scientific Liaison (301) 816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison (301) 816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP38–NF33 Page 5038
Pharmacopeial Forum: Volume No. 39(3)