Propafenone Hydrochloride Extended-Release Capsules
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This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click https://www.uspnf.com/rb/propofenone-hcl-erc-20200806.
1 DEFINITION
Propafenone Hydrochloride Extended-Release Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl).
2 IDENTIFICATION
A.Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K
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
Buffer: Dissolve 1.36 g/L of monobasic potassium phosphate in water, and adjust with phosphoric acid to a pH of 3.0 ± 0.1. Mobile phase: Methanol and Buffer (50:50)
Diluent: 50% methanol in water
Standard solution: 0.1 mg/mL of USP Propafenone Hydrochloride RS in Diluent
Sample stock solution: Nominally 1 mg/mL of propafenone hydrochloride prepared as follows. Transfer a suitable amount of finely powdered contents from NLT 20 Capsules to an appropriate volumetric flask. Add about 60% of the nal volume of Diluent, and sonicate with occasional swirling until the contents are completely disintegrated. Dilute with Diluent to volume and pass through a suitable filter of 0.45- µm pore size.
Sample solution: Nominally 0.1 mg/mL of propafenone hydrochloride in Diluent from the Sample stock solution Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 250 nm
Column: 4.6-mm × 15-cm; 5-µm packing L7
Flow rate: 1 mL/min
Injection volume: 20 µL
Run time: NLT 2 times the retention time of propafenone
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 Capsules 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%
3 PERFORMANCE TESTS
Change to read:
Dissolution 〈711〉
Test 1
Acid stage
Medium: 0.08 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm
Time: 1h
Diluent: 6.8 g/L of monobasic potassium phosphate in water. Adjust with sodium hydroxide to a pH of 6.8.
Standard solution: (L/1000) mg/mL of USP Propafenone Hydrochloride RS in Diluent, where L is the label claim in mg/Capsule Sample solution: At the specified time point, withdraw about 10 mL of the solution and pass through a suitable filter of 0.45-µm pore size. Discard at least the first 4 mL of the filtrate. Analyze the Sample solution immediately.
Instrumental conditions
Mode: UV
Analytical wavelengths: 305 and 375 nm
Cell: 0.2 cm
Blank: Medium
Analysis
Samples: Standard solution and Sample solution
Measure and subtract the absorbance at 375 nm from the absorbance at 305 nm to obtain the absorbances for the Sample solution and Standard solution.
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved:
Result1 = (AU/AS) × (CS/L) × V × 100
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)
L = label claim (mg/Capsule)
V = volume of Medium, 900 mL
Tolerances: See Table 1.
Buffer stage
Proceed as directed in the Acid stage, except for the following parameters.
Buffer: Dissolve 108.88 g of monobasic potassium phosphate in water, add 14.4 g of sodium hydroxide, mix to dissolve, and dilute with water to 1 L. Adjust with 2 N sodium hydroxide to a pH of 6.8.
Solution A: Buffer and 2 N sodium hydroxide (64:36)
Medium: At 2 h of dissolution time, add 100 mL of Solution A, preheated at 37°, to 900 mL of 0.08 N hydrochloric acid. Times: 4 and 12 h
Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (Ci ) of propafenone hydrochloride (C21H27NO3.HCl) in the sample withdrawn from the vessel at each time point (i):
Result1 = (AU/AS) × CS
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at each time point (i):
Result2 = C2 × V × (1/L) × 100
Result3 = {[C3 × (V − VS)] + (C2 × VS)} × (1/L) × 100
Ci = concentration of propafenone hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)
V = volume of Medium, 1000 mL
L = label claim (mg/Capsule)
VS = volume of Medium taken (mL)
Tolerances: See Table 1.
Table 1
Time Point (i) | Time (h) | Amount Dissolved (%) |
| 1 | 1 | 5–25 |
| 2 | 4 | 40–70 |
| 3 | 12 | NLT 75 |
The percentages of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at the times specified conform to
Dissolution 〈711〉, Acceptance Table 2.
Test 2: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2. Acid stage
Acid stage medium: 0.08 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm, with sinkers
Time: 1h
Standard stock solution: 0.42 mg/mL of USP Propafenone Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Propafenone Hydrochloride RS to a suitable volumetric flask. Add methanol, NMT 10% of the nal volume, and sonicate to dissolve. Dilute with Acid stage medium to volume.
Standard solution: 0.021 mg/mL of USP Propafenone Hydrochloride RS in Acid stage medium from the Standard stock solution Sample solution: Pass the solution through a suitable filter of 0.45-µm pore size. Dilute with Acid stage medium to a concentration similar to that of the Standard solution.
Instrumental conditions
Mode: UV
Analytical wavelength: 305 nm
Cell: 1 cm
Blank: Acid stage medium
Analysis
After 1 h in the Acid stage medium and the collection of the Sample solution, replace the portion of solution withdrawn with an equal volume of Acid stage medium. Continue for an additional 1 h in Acid stage medium.
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved:
Result1 = (AU/AS) × CS x D × V × (1/L) x 100
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)
D = dilution factor (mL/mL)
V = volume of Medium, 900 mL
L = label claim (mg/Capsule)
Tolerances: See Table 2.
Buffer stage
Proceed as directed in the Acid stage, except for the following parameters.
Buffer stage medium: After 2 h in the Acid stage, add 100 mL of phosphate buffer (68 g of monobasic potassium phosphate and 42 g of sodium hydroxide in 1000 mL of water), preheated at 37°, to 900 mL of Acid stage medium; 1000 mL.
Times: 6 and 15 h
Standard stock solution: 0.48 mg/mL of USP Propafenone Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Propafenone Hydrochloride RS to a suitable volumetric flask. Add methanol, NMT 10% of the nal volume, and sonicate to dissolve. Dilute with Buffer stage medium to volume.
Standard solution: 0.048 mg/mL of USP Propafenone Hydrochloride RS in Buffer stage medium from Standard stock solution Sample solution: Withdraw a 10-mL aliquot at each time point. Pass the solution through a suitable filter of 0.45-µm pore size. Dilute with Buffer stage medium to a concentration similar to that of the Standard solution.
Blank: Buffer stage medium
Instrumental conditions: See Acid stage.
Analysis
At the specified time points, replace the portion of solution withdrawn with 10 mL of Buffer stage medium.
Samples: Standard solution and Sample solution
Calculate the concentration (Ci ) of propafenone hydrochloride (C21H27NO3.HCl) in the sample withdrawn from the vessel at each time point (i):
Result1 = (AU/AS) × CS x D
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)
D = dilution factor (mL/mL)
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at each time point (i):
Result2 = {[C2 × V] + (C1 × VS)} × (1/L) × 100
Result2 = {[C3 × V] + [(C2 + C1) x VS ]} × (1/L) × 100
Ci = concentration of propafenone hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)
V = volume of Buffer stage medium, 1000 mL
VS = volume Sample solution withdrawn from the Buffer stage medium (mL)
L = label claim (mg/Capsule)
Tolerances: See Table 2.
Table 2
Time Point (i) | Time (h) | Amount Dissolved (%) |
| 1 | 1 | 5–25 |
| 2 | 6 | 45–65 |
| 3 | 15 | NLT 80 |
The percentages of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at the times specified conform to
Dissolution 〈711〉, Acceptance Table 2.
Test 3: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3. Acid stage
Acid stage medium: 0.08 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm, with sinkers
Time: 2 h
Phosphate buffer: Dissolve 190.06 g of tribasic sodium phosphate in 1 L of water.
Diluent: Phosphate buffer and Acid stage medium (12:88). Adjust the pH to 6.8 with phosphoric acid or sodium hydroxide if necessary. Standard solution: (L/1000) mg/mL of USP Propafenone Hydrochloride RS, where L is the label claim in mg/Capsule, prepared as follows. Transfer a suitable amount of USP Propafenone Hydrochloride RS to a suitable volumetric flask. Dissolve with 10% of nal volume of methanol with aid of sonication. Dilute with Diluent to volume.
Sample solution: At the specified time point, withdraw 10 mL of the solution under test and centrifuge. Use the supernatant.
Instrumental conditions Mode: UV
Analytical wavelengths: 305 nm
Cell: 0.2 cm
Blank: Diluent
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved:
Result1 = (AU/AS) × (CS/L) × V × 100
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)
L = label claim (mg/Capsule)
V = volume of Acid stage medium,, 900 mL
Tolerances: See Table 3.
Buffer stage
Proceed as directed in the Acid stage, except for the following parameters.
Buffer stage medium: After the samples are withdrawn at 2 h, add 110 mL or appropriate amount of Phosphate buffer, preheated at 37°, to Acid stage medium, and adjust the pH to 6.8 with phosphoric acid or sodium hydroxide if necessary; 1000 mL. Times: 4 and 12 h
Sample solution: At the specified time points, withdraw 10 mL of the solution and centrifuge. Use the supernatant. Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (Ci ) of propafenone hydrochloride (C21H27NO3.HCl) in the sample withdrawn from the vessel at each time point (i):
Result1 = (AU/AS) × CS
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at each time point (i):
Result2 = {[C2 × (V − VS)] + [C1 × VS]} × (1/L) × 100
Result3 = ({C3 × [V − (2 × VS)]} + [(C2 + C1) × VS]) × (1/L) × 100
Ci = concentration of propafenone hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)
V = volume of Buffer stage medium, 1000 mL
VS = volume of Sample solution withdrawn (mL)
L = label claim (mg/Capsule)
Tolerances: See Table 3.
Table 3
Time Point (i) | Time (h) | Amount Dissolved (%) |
| 1 | 2 | NMT 30 |
| 2 | 4 | 35–60 |
| 3 | 12 | NLT 80 |
The percentages of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at the times specified conform to
Dissolution 〈711〉, Acceptance Table 2.
Test 4: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 4. Acid stage
Acid stage medium: 0.08 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm
Time: 2 h
Diluent: Dissolve 6.8 g of monobasic potassium phosphate with 1 L of water. Adjust with sodium hydroxide to a pH of 6.8. Standard solution: 0.325 mg/mL of USP Propafenone Hydrochloride RS in Diluent
[Note—Sonication may be needed for dissolution.]
Sample solution: At the specified time point, withdraw 5 mL of the solution and pass through a suitable filter. Replace the portion of solution withdrawn with an equal volume of Medium.
Instrumental conditions
Mode: UV
Analytical wavelengths: 305 and 375 nm
Cell: 0.2 cm
Blank: Diluent
Analysis
Samples: Standard solution and Sample solution
Measure and subtract the absorbance at 375 nm from the absorbance at 305 nm to obtain the absorbances for the Sample solution and Standard solution.
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved:
Result1 = (AU/AS) × (CS/L) × V × 100
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)
L = label claim (mg/Capsule)
V = volume of Medium, 900 mL
Tolerances: See Table 4.
Buffer stage
Proceed as directed in the Acid stage, except for the following parameters.
Buffer: Dissolve 108.88 g of monobasic potassium phosphate and 14.4 g of sodium hydroxide with 1 L of water. Adjust with 2 N sodium hydroxide to a pH of 6.8.
Solution A: Buffer and 2 N sodium hydroxide (64:36)
Medium: At 2 h of dissolution time, add 100 mL of Solution A, preheated at 37°, to the vessel containing 900 mL of 0.08 N hydrochloric acid.
Times: 3, 6, and 12 h
Analysis
Samples: Standard solution and Sample solution
Calculate the concentration (Ci ) of propafenone hydrochloride (C21H27NO3.HCl) in the sample withdrawn from the vessel at each time point (i):
Result1 = (AU/AS) × CS
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at each time point (i):
Result2 = [(C2 × V) + (C1 × VS)] × (1/L) × 100
Result3 = {[C3 × V] + [(C2 + C1 ) × VS]} × (1/L) × 100
Result4 = {[C × V] + [(C3 + C2 + C ) × VS]} × (1/L) × 100
Ci = concentration of propafenone hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)
V = volume of Medium, 1000 mL
VS = volume of Medium taken, 5 mL
L = label claim (mg/Capsule)
Tolerances: See Table 4.
Table 4
Time Point (i) | Time (h) | Amount Dissolved (%) |
| 1 | 2 | 15–35 |
| 2 | 3 | 26–46 |
| 3 | 6 | 56–76 |
| 4 | 12 | NLT 80 |
The percentages of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at the times specified conform to
Dissolution 〈711〉, Acceptance Table 2.
Test 5: If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 5. Acid stage
Acid stage medium: 0.08 N hydrochloric acid; 900 mL
Apparatus 2: 50 rpm
Time: 2 h
Diluent: Dissolve 6.8 g of monobasic potassium phosphate with 900 mL of water in a 1-L volumetric flask. Adjust with 2 N sodium hydroxide to a pH of 6.8, and dilute with water to volume.
Standard solution: L/1000 mg/mL of USP Propafenone Hydrochloride RS in Diluent, where L is the label claim. Sonication may be needed for complete dissolution.
Sample solution: At the specified time point, withdraw 10 mL of the solution under test and pass through a suitable filter. Replace the portion of solution withdrawn with an equal volume of Acid stage medium.
Instrumental conditions
Mode: UV
Analytical wavelengths: 305 and 375 nm
Cell: 0.2 cm
Blank: Diluent
Analysis
Samples: Standard solution and Sample solution
Measure and subtract the absorbance at 375 nm from the absorbance at 305 nm to obtain the absorbances for the Sample solution and Standard solution.
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved:
Result1 = (AU/AS) × (CS/L) × V × 100
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of USP Propafenone Hydrochloride RS in the Standard solution (mg/mL)
L = label claim (mg/Capsule)
V = volume of Acid stage medium,, 900 mL
Tolerances: See Table 5.
Buffer stage: Proceed as directed in the Acid stage except for the following parameters.
Buffer: Dissolve 108.88 g of monobasic potassium phosphate in 400 mL of water in a 1-L volumetric flask, and add 14.4 g of sodium hydroxide. Dilute with water to volume, and adjust with 2 N sodium hydroxide to a pH of 6.8.
Solution A: Buffer and 2 N sodium hydroxide (64:36)
Buffer stage medium: At 2 h of dissolution time, add 100 mL of Solution A, preheated at 37°, to the vessel containing 900 mL of 0.08 N hydrochloric acid.
Times: 4 and 10 h
Analysis
Samples: Standard solution and Sample solution
Measure and subtract the absorbance at 375 nm from the absorbance at 305 nm to obtain the absorbances for the Sample solution and Standard solution.
Calculate the concentration (Ci ) of propafenone hydrochloride (C21H27NO3.HCl) in the sample withdrawn from the vessel at each time point (i):
Result1 = (AU/AS) × CS
AU = absorbance of the Sample solution
AS = absorbance of the Standard solution
CS = concentration of the Standard solution (mg/mL)
Calculate the percentage of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at each time point (i):
Result2 = {[C2 × (V − VS)] + [C1 × VS]} × (1/L) × 100
Result = ({C3 × [V − (2 × V )]} + [(C2 + C1) × VS]) × (1/L) × 100
Ci = concentration of propafenone hydrochloride in the portion of sample withdrawn at time point (i) (mg/mL)
V = volume of Buffer stage medium, 1000 mL
VS = volume of sample withdrawn from vessel, 10 mL
L = label claim (mg/Capsule)
Tolerances: See Table 5.
Table 5
Time Point (i) | Time (h) | Amount Dissolved (%) |
| 1 | 2 | 15–35 |
| 2 | 4 | 39–59 |
| 3 | 10 | NLT 80 |
The percentages of the labeled amount of propafenone hydrochloride (C21H27NO3.HCl) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
Uniformity of Dosage Units 〈905〉: Meet the requirements
4 IMPURITIES
Change to read:
Organic Impurities
Keep all solutions containing propafenone hydrochloride in amber glassware.
Solution A: 0.015 M dibasic potassium phosphate. Adjust with phosphoric acid to a pH of 2.5 ± 0.2.
Solution B: Acetonitrile
Mobile phase: See Table 6.
Table 6
Time (min) | Solution A (%) | Solution B (%) |
| 0 | 65 | 35 |
| 8 | 65 | 35 |
| 20 | 30 | 70 |
| 30 | 30 | 70 |
| 31 | 65 | 35 |
| 36 | 65 | 35 |
Diluent: 50% methanol in water
System suitability solution: 0.1 mg/mL each of USP Propafenone Hydrochloride RS and USP Propafenone Related Compound B RS in Diluent Standard solution: 2.0 µg/mL of USP Propafenone Hydrochloride RS in Diluent. Sonicate if necessary.
Sensitivity solution: 0.3 µg/mL of USP Propafenone Hydrochloride RS in Diluent from the Standard solution
Sample solution: Nominally 1 mg/mL of propafenone hydrochloride, prepared as follows. Transfer a suitable amount of finely powdered contents from NLT 20 Capsules to an appropriate volumetric flask. Add about 40% of the nal volume of Diluent and sonicate for about 15 min. Dilute with Diluent to volume and pass through a suitable filter of 0.45-µm pore size.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
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, Standard solution, and Sensitivity solution
Suitability requirements
Resolution: NLT 3.0 between propafenone related compound B and propafenone, System suitability solution
Relative standard deviation: NMT 5.0%, Standard solution
Signal-to-noise ratio: NLT 10, Sensitivity solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each individual unspecified degradation product in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of each unspecified degradation product 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: See Table 7. Disregard any peaks below 0.03% (peak area less than that of the Sensitivity solution). Table 7
| Name | Relative Retention Time | Acceptance Criteria, NMT (%) |
| compound Ba,b Propafenone related | 0.81 | — |
| Propafenone | 1.00 | — |
Propafenone Glycerol analoga,c | 2.53 | — |
| Flavonea,d | 2.83 | — |
| Propafenone dimera,e | 2.88 | — |
Propafenone chloroglycerol analoga,f | 2.91 | — |
Propafenone glycidyl analoga,g | 2.96 | — |
| Propafenone phenola,h | 3.29 | — |
| Propafenone glycerol dimera,i | 3.80 | — |
Any unspecified degradation product | — | 0.15 |
Total degradation products | — | 0.50 |
a Process impurities; do not include in total degradation products.
b (RS,E)-1-{2-[2-Hydroxy-3-(propylamino)propoxy]phenyl}-3-phenylprop-2-en-1-one.
c 1-[2-[(2RS)-2,3-Dihydroxypropoxy]phenyl]-3-phenylpropan-1-one.
d 2-Phenylchroman-4-one.
e 1,1'-[Propyliminobis(2-hydroxypropane-3,1-diyl)oxy-2,1-phenylene]bis(3-phenylpropan-1-one).
f 1-[2-(3-Chloro-2-hydroxypropoxy)phenyl]-3-phenylpropan-1-one.
g 1-[2-[[(RS)-Oxiranyl]methoxy]phenyl]-3-phenylpropan-1-one.
h 1-(2-Hydroxyphenyl)-3-phenylpropan-1-one.
i 1,1'-(2,2'-(2-Hydroxypropane-1,3-diyl)bis(oxy)bis(2,1-phenylene))bis(3-phenylpropan-1-one).
Change to read:
Content of Propafenone Related Compound A
Buffer: Dissolve 3.4 g of dibasic potassium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 2.5 ± 0.05. Solution A: Methanol and Buffer (45:55); pass through a suitable filter of 0.2-µm pore size.
Solution B: Methanol and Buffer (75:25); pass through a suitable filter of 0.2-µm pore size.
Mobile phase: See Table 8.
Table 8
Time (min) | Solution A (%) | Solution B (%) |
| 0 | 100 | 0 |
| 4.0 | 100 | 0 |
| 7.0 | 50 | 50 |
| 10.0 | 0 | 100 |
| 12.0 | 0 | 100 |
| 12.5 | 100 | 0 |
| 15.0 | 100 | 0 |
Diluent: Methanol and water (80:20)
Standard solution: 2.0 µg/mL of USP Propafenone Related Compound A RS in Diluent
Sensitivity solution: 0.2 µg/mL of USP Propafenone Related Compound A RS in Diluent from the Standard solution
Sample solution: Nominally 1 mg/mL of propafenone hydrochloride prepared as follows. Transfer a suitable amount of finely powdered contents from NLT 20 Capsules to an appropriate volumetric flask. Add about 75% of the nal volume of Diluent and sonicate with intermittent shaking for 20 min. Dilute with Diluent to volume and pass through a suitable filter of 0.45-µm pore size. Discard the first 4 mL of the filtrate.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 250 nm
Column: 2.1-mm × 10-cm; 1.7-µm packing L1
Column temperature: 60°
Flow rate: 0.4 mL/min
Injection volume: 4 µL
System suitability
Samples: Standard solution and Sensitivity solution
Suitability requirements
Tailing factor: NMT 2.0, Standard solution
Relative standard deviation: NMT 6.0%, Standard solution
Signal-to-noise ratio: NLT 10, Sensitivity solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of propafenone related compound A in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response of propafenone related compound A from the Sample solution
rS = peak response of propafenone related compound A from the Standard solution
CS = concentration of USP Propafenone related compound A RS in the Standard solution (mg/mL)
CU = nominal concentration of propafenone hydrochloride in the Sample solution (mg/mL)
Acceptance criteria: See Table 9.
Table 9
| Name | Relative Retention Time | Acceptance Criteria, NMT (%) |
| Propafenone | 1.0 | — |
| compound Aa Propafenone related | 1.9 | 0.20 |
a N-{2-Hydroxy-3-[2-(3-phenylpropanoyl)phenoxy]propyl}-N-propylformamide.
5 ADDITIONAL REQUIREMENTS
Packaging and Storage: Keep in tight containers and store at controlled room temperature.
Labeling: When more than one test for Dissolution is given, the Labeling section states the test for Dissolution used only if Test 1 is not used. USP Reference Standards 〈11〉
USP Propafenone Hydrochloride RS
USP Propafenone Related Compound A RS
N-{2-Hydroxy-3-[2-(3-phenylpropanoyl)phenoxy]propyl}-N-propylformamide.
C22H27NO4 369.45
USP Propafenone Related Compound B RS
(RS,E)-1-{2-[2-Hydroxy-3-(propylamino)propoxy]phenyl}-3-phenylprop-2-en-1-one.
C21H25NO3 339.43
