Paroxetine Extended-Release Tablets
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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.
1 DEFINITION
Paroxetine Extended-Release Tablets contain paroxetine hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of paroxetine (C19H20FNO3).
2 IDENTIFICATION
A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
3 ASSAY
Procedure
Buffer: 3.9 g/L of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.5.
Mobile phase: Acetonitrile, Buffer, and triethylamine (40:60:1). Adjust with glacial acetic acid to a pH of 5.5.
Standard solution: 0.5 mg/mL of USP Paroxetine Hydrochloride RS in methanol
System suitability solution: 0.5 mg/mL of USP Paroxetine Related Compound B RS in Standard solution
Sample solution: Nominally 0.5 mg/mL of paroxetine from NLT 10 Tablets prepared as follows. Transfer the required number of Tablets to a suitable volumetric flask. Add 80% of the ask volume of methanol. Sonicate for 30 min followed by stirring for 30 min. Dilute with methanol to volume.
3.1 Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 295 nm
Column: 4.6-mm × 25-cm; 5-µm packing L13
Flow rate: 1 mL/min
Injection volume: 10 µL
3.2 System suitability
Samples: Standard solution and System suitability solution
[Note—The relative retention times for paroxetine related compound B and paroxetine are 0.9 and 1.0, respectively.] Suitability requirements
Resolution: NLT 1.5 between paroxetine related compound B and paroxetine, System suitability solution
Tailing factor: NMT 2.0 for paroxetine, System suitability solution
Relative standard deviation: NMT 2.0% for paroxetine, Standard solution
3.3 Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) in the portion of Tablets taken:
Result = (rU /rS ) × (CS /CU) × (Mr1 /Mr2) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Standard solution (mg/mL)
CU = nominal concentration of paroxetine in the Sample solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
Acceptance criteria: 90.0%–110.0%
4 PERFORMANCE TESTS
Change to read:
Dissolution 〈711〉
4.1 Test 1
Acid stage medium: 0.1 N hydrochloric acid; 750 mL
Buffer stage medium: 0.05 M tris buffer prepared as follows. Dissolve 6.06 g of tris(hydroxymethyl)aminomethane in 1 L of water. Add 1.8 mL of hydrochloric acid to the resulting solution. Adjust with hydrochloric acid to a pH of 7.5; 1000 mL deaerated.
Apparatus 1: 100 rpm
Times: 2 h in Acid stage; 2, 4, and 12 h in Buffer stage
Buffer and Mobile phase: Proceed as directed in the Assay.
Acid stage standard stock solution: 0.33 mg/mL of paroxetine prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Dissolve in 5% of the ask volume of methanol. Dilute with Acid stage medium to volume. Acid stage standard solution: Dilute the Acid stage standard stock solution with Acid stage medium to obtain a nal concentration of (L/7500) mg/mL, where L is the label claim in mg.
Buffer stage standard stock solution: 0.25 mg/mL of paroxetine prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Dissolve in 5% of the ask volume of methanol. Dilute with Buffer stage medium to volume.
Buffer stage standard solution: Dilute the Buffer stage standard stock solution with Buffer stage medium to obtain a nal concentration of (L/1000) mg/mL, where L is the label claim in mg.
Acid stage sample solution: Run the Acid stage for 2 h. Withdraw 10 mL of the solution under test and centrifuge. Use the centrifugate for analysis.
Buffer stage sample solution: Remove the Acid stage medium from the vessel and replace it with the Buffer stage medium. At the times specified, remove 10 mL of the solution under test and centrifuge. Use the centrifugate for analysis.
Chromatographic system: Proceed as directed in the Assay. For Injection volume, use 100 µL for the Acid stage analysis and 10 µL for the Buffer stage analysis.
4.1.1 System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2.0, Acid stage standard solution and Buffer stage standard solution
Relative standard deviation: NMT 3.0%, Acid stage standard solution and Buffer stage standard solution
4.1.2 Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved in the Acid stage:
Result = (rU /rS ) × CS × (Mr1 /Mr2) × V × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Acid stage standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Acid stage standard solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
M = molecular weight of paroxetine hydrochloride, 365.83
V = volume of the Acid stage medium, 750 mL
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of paroxetine (C19H20FNO3) dissolved at each time point in the Buffer stage:
Result = (ri /rS ) × CS × (Mr1 /Mr2 )
ri = peak response from the Buffer stage sample solution at each time point i
rS = peak response from the Buffer stage standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Buffer stage standard solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
Calculate the percentage of the labeled amount (Qi) of paroxetine (C19H20FNO3) dissolved at each time point (i) in the Buffer stage medium:
Result1 = C1 × V × (1/L) × 100
Result2 = {[C2 × (V − VS )] + (C1 × V )} × (1/L) × 100
Result3 = ({C3 × [V − (2 × VS )]} + [(C2 + C1 ) × V ]) × (1/L) × 100
Ci = concentration of paroxetine in the Buffer stage medium in the portion of sample withdrawn at time point i (mg/mL) i
V = volume of the Buffer stage medium, 1000 mL
L = label claim (mg/Tablet)
VS = volume of the Sample solution withdrawn from the Buffer stage medium (mL)
Tolerances
Acid stage: NMT 10% of the labeled amount of paroxetine (C19H20FNO3) is dissolved in 2 h.
Buffer stage: See Table 1.
Table 1
Time Point (i) | Time (h) | Amount Dissolved (Tablets labeled to contain 12.5 mg of paroxetine) | Amount Dissolved (Tablets labeled to contain 25 mg of paroxetine) | Amount Dissolved (Tablets labeled to contain 37.5 mg of paroxetine) |
1 | 2 | 15%–35% | 10%–30% | 20%–45% |
2 | 4 | 40%–70% | 40%–70% | 60%–85% |
3 | 12 | NLT 80% | NLT 80% | NLT 80% |
The percentages of the labeled amount of paroxetine (C19H20FNO3) dissolved at the times specied conform to Dissolution 〈711〉,
Acceptance Table 2.
4.2 Test 2
If the product complies with this procedure, the labeling indicates that it meets USP Dissolution Test 2.
Acid stage medium: 0.1 N hydrochloric acid; 750 mL
Buffer stage medium: 0.05 M tris buffer prepared as follows. Dissolve 6.06 g of tris(hydroxymethyl)aminomethane in 900 mL of water. Add 40 mL of 1.0 M hydrochloric acid to the resulting solution. Adjust with either 1.0 M hydrochloric acid or 1.0 M sodium hydroxide to a pH of 7.5. Dilute with water to 1 L; 1000 mL deaerated.
Apparatus 2: 150 rpm with suitable sinkers
Times: 2 h in Acid stage; 1, 2, 4, and 6 h in Buffer stage
Acid stage standard stock solution: 0.04 mg/mL of USP Paroxetine Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Dissolve in 2 mL of methanol. Dilute with Acid stage medium to volume.
Acid stage standard solution: Dilute the Acid stage standard stock solution with Acid stage medium to obtain a nal concentration of (L/7500) mg/mL of paroxetine, where L is the label claim in mg.
Buffer stage standard solution: (L/1000) mg/mL of paroxetine, where L is the label claim in mg prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Dissolve in 2 mL of methanol. Dilute with Buffer stage medium to volume.
Acid stage sample solution: Run the Acid stage for 2 h. Withdraw 10 mL of the solution under test, and filter. Use the filtrate for analysis. Buffer stage sample solution: Remove the Tablet and sinker from the acid stage vessel and pat them dry. Introduce the Tablet and sinker into the dissolution vessel with 1000 mL of the Buffer stage medium. At the times specified, remove 10 mL of the solution under test and filter. Use the filtrate for analysis.
4.2.1 Acid stage analysis
Buffer: Add 2.9 mL of phosphoric acid to 800 mL of water. Adjust with 1 M sodium hydroxide to a pH of 6.0. Dilute with water to 1000 mL. Mobile phase: Acetonitrile and Buffer (40:60)
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 205 nm
Column: 4.6-mm × 25-cm; 5-µm packing L1
Flow rate: 2 mL/min
Injection volume: 50 µL for 12.5-mg Tablet; 20 µL for 25- and 37.5-mg Tablets
Run time: 2 times the retention time of paroxetine
System suitability
Sample: Acid stage standard solution
Suitability requirements
Tailing factor: NMT 2.0
Relative standard deviation: NMT 2.0%
Analysis
Samples: Acid stage standard solution and Acid stage sample solution
Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved in the Acid stage:
Result = (rU /rS ) × CS × (Mr1 /Mr2) × V × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Acid stage standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Acid stage standard solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
V = volume of the Acid stage medium, 750 mL
L = label claim (mg/Tablet)
4.2.2 Buffer stage analysis
Instrumental conditions
Mode: UV
Analytical wavelength: 294 nm with 340 nm for background correction
Blank: Buffer stage medium
Analysis
Samples: Buffer stage standard solution and Buffer stage sample solution
Calculate the concentration (Ci) of paroxetine (C19H20FNO3) dissolved at each time point (i) in the Buffer stage:
Result = (Ai/AS ) × CS × (Mr1 /Mr2 )
Ai = absorbance of the Buffer stage sample solution at time point i
AS = absorbance of the Buffer stage standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Buffer stage standard solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved at each time point (i) in the Buffer stage medium:
Result1 = C1 × V × (1/L) × 100
Result2 = {[C2 × (V − VS )] + (C1 × VS )} × (1/L) × 100
Result3 = ({C3 × [V − (2 × VS )]} + [(C2 + C1 ) × VS ]) × (1/L) × 100
Result4 = ({C4 × [V − (3 × VS )]} + [(C3 + C2 + C1 ) × VS ]) × (1/L) × 100
Ci = concentration of paroxetine in the Buffer stage medium in the portion of sample withdrawn at time point i (mg/mL)
V = volume of the Buffer stage medium, 1000 mL
L = label claim (mg/Tablet)
VS = volume of the Sample solution withdrawn from the Buffer stage medium (mL)
Tolerances
Acid stage: NMT 10% of the labeled amount of paroxetine (C19H20FNO3) is dissolved in 2 h.
Buffer stage: See Table 2.
Table 2
Time Point (i) | Time (h) | Amount Dissolved |
1 | 1 | NMT 20% |
2 | 2 | 20%–45% |
3 | 4 | 60%–90% |
4 | 6 | NLT 85% |
The percentages of the labeled amount of paroxetine (C19H20FNO3) dissolved at the times specified conform to Dissolution 〈711〉, Acceptance Table 2.
4.3 Test 3
If the product complies with this procedure, the labeling indicates that it meets USP Dissolution Test 3.
Acid stage medium: 0.1 N hydrochloric acid; 750 mL
Buffer stage medium: 0.05 M tris buffer prepared as follows. Dissolve 42 g of tris(hydroxymethyl)aminomethane in 2000 mL of water. Pass through a suitable filter of 0.45-µm pore size. Add 5000 mL of water and adjust with hydrochloric acid to a pH of 7.5; 1000 mL deaerated. Apparatus 2: 150 rpm with suitable sinkers
Times: 2 h in Acid stage; 2, 4, and 6 h in Buffer stage
Solution A: 1.36 g/L of potassium phosphate monobasic and 2.44 g/L of sodium 1-decanesulfonate in water. Adjust with 0.5% phosphoric acid to a pH of 3.0.
Mobile phase: Acetonitrile and Solution A (45:55)
Standard stock solution: 0.042 mg/mL of USP Paroxetine Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Add about 50% of the nal flask volume of Buffer stage medium and sonicate for about 15 min to dissolve. Dilute with Buffer stage medium to volume.
Standard solution: 0.021 mg/mL of USP Paroxetine Hydrochloride RS prepared as follows. Mix equal portions of Standard stock solution and Acid stage medium in a suitable glass container.
Acid stage sample solution: Run the Acid stage for 2 h. Withdraw 10 mL of the solution under test. Centrifuge to obtain a clear supernatant. Mix equal portions of the supernatant and Acid stage medium in a suitable glass container. Use the resulting solution for analysis. Buffer stage sample solution: Remove the Tablet in the sinker from the acid stage vessel. Add the Tablet in the sinker to the vessel with 1000 mL of Buffer stage medium and run the Buffer stage. At the times specified, remove 10 mL of the solution under test. Centrifuge to obtain a clear supernatant. Mix equal portions of the supernatant and Acid stage medium in a suitable glass container. Use the resulting solution for analysis.
4.3.1 Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 235 nm
Column: 4.6-mm × 15-cm; 5-µm packing L1
Column temperature: 30°
Flow rate: 1 mL/min
Injection volume: 50 µL
Run time: About 1.5 times the retention time of paroxetine
4.3.2 System suitability
Sample: Standard solution
Suitability requirements
Tailing factor: NMT 2
Relative standard deviation: NMT 2.0%
4.3.3 Analysis
Samples: Standard solution, Acid stage sample solution, and Buffer stage sample solution
Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved in the Acid stage:
Result = (rU /rS ) × CS × (Mr1 /Mr2) × D × V × (1/L) × 100
rU = peak response from the Acid stage sample solution
rS = peak response from the Standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Standard solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
D = dilution factor
V = volume of the Acid stage medium, 750 mL
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of paroxetine (C19H20FNO3 ) dissolved at each time point (i) in the Buffer stage:
Resulti = (ri /rS ) × CS × (Mr1 /Mr2) × D
ri = peak response from the Buffer stage sample solution at time point i
rS = peak response from the Standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Standard solution (mg/mL)
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
D = dilution factor
Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved at each time point (i) in the Buffer stage medium:
Result1 = C1 × V × (1/L) × 100
Result2 = {[C2 × (V − VS )] + (C1 × V )} × (1/L) × 100
Result3 = ({C3 × [V − (2 × VS )]} + [(C2 + C1 ) × V ]) × (1/L) × 100
Ci = concentration of paroxetine in the Buffer stage medium in the portion of sample withdrawn at time point i (mg/mL)
V = volume of the Buffer stage medium, 1000 mL
L = label claim (mg/Tablet)
VS = volume of the sample solution withdrawn from the Buffer stage medium (mL)
4.3.4 Tolerances
Acid stage: NMT 10% of the labeled amount of paroxetine (C19H20FNO3) is dissolved.
Buffer stage: See Table 3.
Table 3
Time Point (i) | Time (h) | Amount Dissolved (%) |
1 | 2 | 20–50 |
2 | 4 | 55–85 |
3 | 6 | NLT 80 |
The percentages of the labeled amount of paroxetine (C19H20FNO3) dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2.
4.4 Test 4
If the product complies with this procedure, the labeling indicates that it meets USP Dissolution Test 4.
Acid stage medium: 0.1 N hydrochloric acid; 750 mL
Buffer stage medium: 6.05 g/L of tris(hydroxymethyl)aminomethane in water. Adjust with hydrochloric acid to a pH of 7.5; 1000 mL. Apparatus 2: 150 rpm
Times: 2 h in Acid stage; 2, 4, and 8 h in Buffer stage
Solution A: 3.85 g/L of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.5.
Mobile phase: Acetonitrile, Solution A, and triethylamine (35:65:1). Adjust with glacial acetic acid to a pH of 5.5.
Acid stage standard stock solution: 0.190 mg/mL of USP Paroxetine Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Add 4% of the ask volume of methanol and sonicate to dissolve. Dilute with Acid stage medium to volume.
Acid stage standard solution: 0.019 mg/mL of USP Paroxetine Hydrochloride RS from Acid stage standard stock solution in Acid stage medium
Buffer stage standard stock solution: 0.142 mg/mL of USP Paroxetine Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Paroxetine Hydrochloride RS to a suitable volumetric flask. Add 4% of the ask volume of methanol and sonicate to dissolve. Dilute with Buffer stage medium to volume.
Buffer stage standard solution: 0.0142 mg/mL of USP Paroxetine Hydrochloride RS from Buffer stage standard stock solution in Buffer stage medium
Acid stage sample solution: At the time specified, withdraw 10 mL of the solution under test and pass through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of filtrate. Dilute, if needed, with Acid stage medium to a concentration that is similar to that of the Acid stage standard solution.
Buffer stage sample solution: Remove the Acid stage medium from the vessel and replace it with the Buffer stage medium. At the times specified, withdraw 10 mL of the solution under test and replace with 10 mL of Buffer stage medium. Pass the solution under test through a suitable filter of 0.45-μm pore size, discarding the first 2–3 mL of filtrate. Dilute, if needed, with Buffer stage medium to a concentration that is similar to that of the Buffer stage standard solution.
4.4.1 Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 295 nm
Column: 4.6-mm × 15-cm; 3-µm packing L1
Temperatures
Autosampler: 10°
Column: 35°
Flow rate: 1.2 mL/min
Injection volume: 100 µL
Run time: NLT 2 times the retention time of paroxetine
4.4.2 System suitability
Samples: Acid stage standard solution and Buffer stage standard solution
Suitability requirements
Tailing factor: NMT 2, Acid stage standard solution and Buffer stage standard solution
Relative standard deviation: NMT 2.0%, Acid stage standard solution and Buffer stage standard solution
4.4.3 Analysis
Samples: Acid stage standard solution, Buffer stage standard solution, Acid stage sample solution, and Buffer stage sample solution Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved in the Acid stage (QA):
Result = (rU /rS) × CS × V × D × (Mr1 /Mr2) × (1/L) × 100
rU = peak response of paroxetine from the Acid stage sample solution
rS = peak response of paroxetine from the Acid stage standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Acid stage standard solution (mg/mL)
V = volume of the Acid stage medium, 750 mL
D = dilution factor for the Acid stage sample solution
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
L = label claim (mg/Tablet)
Calculate the concentration (Ci) of paroxetine (C19H20FNO3) in the sample withdrawn from the vessel at each time point (i) in the Buffer stage:
Resulti = (ri /rS ) × CS × D × (Mr1 /Mr2 )
ri = peak response of paroxetine from the Buffer stage sample solution
rS = peak response of paroxetine from the Buffer stage standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Buffer stage standard solution (mg/mL)
D = dilution factor for the Buffer stage sample solution
Mr1 = molecular weight of paroxetine, 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
Calculate the percentage of the labeled amount of paroxetine (C19H20FNO3) dissolved at each time point (i) in the Buffer stage:
Result1 = C1 × V × (1/L) × 100 + QA
Result2 = [(C2 × V) + (C1 × VS )] × (1/L) × 100 + QA
Result3 = {(C3 × V) + [(C2 + C1 ) × VS ]} × (1/L) × 100 + QA
C = concentration of paroxetine in the portion of sample withdrawn at time point i (mg/mL)
V = volume of the Buffer stage medium, 1000 mL
L = label claim (mg/Tablet)
QA = percentage of the labeled amount of paroxetine dissolved in the Acid stage
VS = volume of the sample solution withdrawn at each time point and replaced with Buffer stage medium (mL)
4.4.4 Tolerances
Acid stage: NMT 25% of the labeled amount of paroxetine (C19H20FNO3) is dissolved.
Buffer stage: See Table 4.
Table 4
Time Point (i) | Time (h) | Amount Dissolved (%) |
1 | 2 | 23–43 |
2 | 4 | 50–70 |
3 | 8 | NLT 80 |
The percentages of the labeled amount of paroxetine (C19H20FNO3) dissolved at the times specied conform to Dissolution 〈711〉, Acceptance Table 2. (RB 1-Aug-2022)
Uniformity of Dosage Units 〈905〉: Meet the requirements
5 IMPURITIES
Change to read:
Organic Impurities
Solution A: Tetrahydrofuran, water, and trifluoroacetic acid (20:180:1)
Solution B: Acetonitrile, tetrahydrofuran, and trifluoroacetic acid (180:20:1)
Mobile phase: See Table 5.
Table 5 (RB 1-Aug-2022)
Time (min) | Solution A (%) | Solution B (%) |
0 | 80 | 20 |
30 | 80 | 20 |
50 | 20 | 80 |
60 | 20 | 80 |
70 | 80 | 20 |
80 | 80 | 20 |
System suitability solution: 1 mg/mL of USP Paroxetine Hydrochloride RS, 0.1 mg/mL of USP Paroxetine System Suitability Mixture A RS, and 1 mg/mL of USP Paroxetine Related Compound F RS in methanol. [Note—Sonication may be used to aid dissolution of the individual components.]
Standard solution: 0.01 mg/mL of USP Paroxetine Hydrochloride RS in methanol
Sample solution: Nominally 1 mg/mL of paroxetine from NLT 10 Tablets prepared as follows. Transfer a suitable number of Tablets to a suitable volumetric flask. Add 50% of the ask volume of methanol. Sonicate for 30 min followed by stirring for 30 min. Dilute with methanol to volume. Mix and centrifuge. Use the clear centrifugate.
5.1 Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 285 nm
Column: 4.6-mm × 25-cm; 5-µm packing L7
Column temperature: 40°
Flow rate: 1 mL/min
Injection volume: 20 µL
5.2 System suitability
Samples: System suitability solution and Standard solution
[Note—See
Table 6 (RB 1-Aug-2022) for the relative retention times.]
Suitability requirements
Resolution: NLT 1.5 between paroxetine related compound A and paroxetine related compound B; NLT 1.5 between paroxetine related compound F and paroxetine, System suitability solution
Tailing factor: NMT 2.0 for paroxetine, Standard solution
Relative standard deviation: NMT 5.0% for paroxetine, Standard solution
5.3 Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU /rS ) × (CS /CU) × (Mr1 /Mr2) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Paroxetine Hydrochloride RS in the Standard solution (mg/mL)
CU = nominal concentration of paroxetine in the Sample solution (mg/mL)
Mr1 = molecular weight of paroxetine 329.37
Mr2 = molecular weight of paroxetine hydrochloride, 365.83
Acceptance criteria: See Table 6.
Table 6 (RB 1-Aug-2022)
Name | Relative Retention Time | Acceptance Criteria, NMT (%) |
compound Aa OParoxetine related | 0.67 | — |
Paroxetine related compound Ba | 0.75 | — |
Paroxetine related compound Fa | 0.90 | — |
Paroxetine | 1.0 | — |
Ethoxyparoxetineb | 1.2 | 0.2 |
Any unspecified degradation product | — | 0.2 |
Total impurities | — | 1.0 |
a Process impurities, included for identification only. Process impurities are controlled in the drug substance and are not to be reported or included in the total impurities of the drug product.
b (3SR,4RS)-3-(1,3-Benzodioxol-5-yloxy)methyl)-4-(4-ethoxyphenyl)piperidine.
6 ADDITIONAL REQUIREMENTS
Packaging and Storage: Preserve in well-closed containers at controlled room temperature.
Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
USP Reference Standards 〈11〉
USP Paroxetine Hydrochloride RS
USP Paroxetine Related Compound B RS
trans-4-Phenyl-3-[(3,4-methylenedioxy)phenoxy]methylpiperidine hydrochloride;
Also known as Piperidine, 3-[(1,3-benzodioxol-5-yloxy)methyl]-4-phenyl-, hydrochloride (3S-trans).
C19H21NO3 · HCl 347.84
USP Paroxetine Related Compound F RS
(3S,4R)-3-[(Benzodioxol-5-yloxy)methyl]-4-(4-uorophenyl)-1-methylpiperidine.
C20H22FNO3 343.39
USP Paroxetine System Suitability Mixture A RS
Mixture of approximately 1% paroxetine related compound A [piperidine, 3-[(1,3-benzodioxol-5-yloxy)methyl]-4-(4-methoxyphenyl)-, hydrochloride (3S-trans)], and 1% paroxetine related compound B [piperidine, 3-[(1,3-benzodioxol-5-yloxy)methyl]-4-phenyl-, hydrochloride (3S trans)] in a matrix of paroxetine hydrochloride.
