Ropinirole Tablets
DEFINITION
Ropinirole Tablets contain ropinirole hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ropinirole free base (C16H24N2O).
IDENTIFICATION
• 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:
3.85 g/L of ammonium acetate. Adjust with phosphoric acid to a pH of 2.5.
Mobile phase:
Acetonitrile, methanol, and Buffer (7:3:40)
System suitability solution:
0.1 mg/mL of USP Ropinirole Hydrochloride RS and 0.5 µg/mL of USP Ropinirole Related Compound B RS in Buffer
Standard solution:
0.1 mg/mL of USP Ropinirole Hydrochloride RS in Buffer
Sample solution:
Nominally 0.1 mg/mL of ropinrole in Buffer (from NLT 5 Tablets) prepared as follows: Add 50% of the flask volume with Buffer. Shake mechanically for 30 min. Dilute with Buffer to volume. Pass a portion of the supernatant through a suitable membrane filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Column temperature:
30
Flow rate:
1 mL/min
Injection size:
20 µL
Run time:
2 times the retention time of the ropinirole peak
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between ropinirole and ropinirole related compound B; System suitability solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of ropinirole (C16H24N2O) in the portion of Tablets taken:
Result = (rU/rS) × (CS/CU) × (Mr1/Mr2) × 100
| rU | = | = peak response of the Sample solution |
| rS | = | = peak response of the Standard solution |
| CS | = | = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = nominal concentration of ropinirole in the Sample solution (mg/mL) |
| Mr1 | = | = molecular weight of ropinirole, 260.37 |
| Mr2 | = | = molecular weight of ropinirole hydrochloride, 296.84 |
Acceptance criteria:
90.0%–110.0% of ropinirole free base
PERFORMANCE TESTS
• Dissolution 
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Test 1
Medium:
2.9 g/L of sodium citrate dihydrate and 3.3 g/L of anhydrous citric acid in water, pH 4.0; 500 mL
Apparatus 1:
50 rpm
Time:
15 min
Mobile phase:
Acetonitrile and Medium (1:4)
Standard solution:
4.5 µg/mL of USP Ropinirole Hydrochloride RS in Medium
Sample solution:
Pass a portion of the solution through a suitable filter of 0.45-µm pore size, discarding the first few mL. Dilute with Medium to a concentration similar to the Standard solution.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
3.0-mm × 7-cm; 5-µm packing L1
Flow rate:
0.6 mL/min
Injection size:
50 µL
Run time:
3 times the retention time of the ropinirole 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 ropinirole dissolved:
Result = (rU/rS) × (CS/L) × D × (Mr1/Mr2) × V × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL) |
| L | = | = Tablet label claim (mg) |
| D | = | = dilution factor of the Sample solution |
| Mr1 | = | = molecular weight of ropinirole, 260.37 |
| Mr2 | = | = molecular weight of ropinirole hydrochloride, 296.84 |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 85% (Q) of the labeled amount of ropinirole is dissolved.
Test 2:
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
2.1 g/L of citric acid in water. Adjust with a solution containing 121.2 g/L of tris (hydroxymethyl)methylamine in water to a pH of 4.0 ± 0.1; 500 mL, deaerated.
Apparatus 1:
50 rpm
Time:
15 min
Standard solution:
L/500 (µg/mL) of USP Ropinirole Hydrochloride RS in Medium, in which L is the label claim in mg/Tablet
Buffer and Mobile phase:
Prepare as directed in the Assay.
Sample solution:
Pass a portion of the solution through a polyethylene filter of 15- to 20-µm pore size, discarding the first few mL.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6-mm × 25-cm; 5-µm packing L7
Flow rate:
1.0 mL/min
Injection size:
200 µL for Tablets with a label claim of 0.25, 0.5, 1.0, and 2.0 mg/Tablet; 100 µL for all other strengths
System suitability
Sample:
Standard solution
Suitability requirements
Relative standard deviation:
NMT 1.5%
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of ropinirole (C16H24N2O) dissolved:
Result = (rU/rS) × (CS/L) × (Mr1/Mr2) × V × 100
| rU | = | = peak response of the Sample solution |
| rS | = | = peak response of the Standard solution |
| CS | = | = concentration of USP Ropinirole Hydrochloride RS in the Standard solution (mg/mL) |
| Mr1 | = | = molecular weight of ropinirole, 260.37 |
| Mr2 | = | = molecular weight of ropinirole hydrochloride, 296.84 |
| V | = | = volume of Medium, 500 mL |
Tolerances:
NLT 80% (Q) of the labeled amount of ropinirole is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Solution A:
3.85 g/L of ammonium acetate. Adjust with phosphoric acid to a pH of 2.5.
Solution B:
Methanol and acetonitrile (3:7)
Mobile phase:
See the gradient table below.
| Time (min) |
Solution A (%) |
Solution B (%) |
|---|---|---|
| 0 | 84 | 16 |
| 16 | 84 | 16 |
| 36 | 20 | 80 |
| 36.1 | 84 | 16 |
| 51 | 84 | 16 |
System suitability solution:
0.1 mg/mL of USP Ropinirole Hydrochloride RS and 0.5 µg/mL of USP Ropinirole Related Compound B RS in Buffer
Standard solution:
0.1 mg/mL of USP Ropinirole Hydrochloride RS in Buffer
Sample solution:
0.1 mg/mL of ropinirole in Buffer (from NLT 5 Tablets) prepared as follows: Add 50% of the flask volume with Buffer. Shake mechanically for 30 min. Dilute with Buffer to volume. Pass a portion of the supernatant through a suitable membrane filter of 0.45-µm pore size.
Chromatographic system
Mode:
LC
Detector:
UV 250 nm
Column:
4.6 mm × 25 cm; 5-µm packing L7
Flow rate:
1 mL/min
Injection size:
100 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between ropinirole and ropinirole related compound B, System suitability solution
Relative standard deviation:
NMT 1.5%, Standard solution
Analysis
Sample:
Sample solution
Calculate the percentage of each impurity in the portion of Tablets taken:
Result = (rU/rT) × 100
| rU | = | = peak area for the individual impurity from the Sample solution |
| rT | = | = sum of all peak areas from the Sample solution |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 2.0%
Impurity Table 1
| Name | Relative Retention Time |
Acceptance Criteria, NMT (%) |
|---|---|---|
| Monopropyl ropinirolea | 0.4 | 0.6 |
| Ropinirole related compound Bb | 0.9 | 0.6 |
| Ropinirole | 1.0 | — |
| Propylidene ropinirolec | 2.2 | 0.4 |
| Any unspecified degradation product | — | 0.3 |
|
a
4-[2-(Propylamino)ethyl]indolin-2-one.
b
4-[2-(Dipropylamino)ethyl]indoline-2,3-dione.
c
(Z)-4-[2-(Dipropylamino)ethyl]-3-propylideneindolin-2-one.
|
||
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store 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
11
USP Ropinirole Hydrochloride RS 
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USP Ropinirole Related Compound B RS
[4-[2-(Dipropylamino)ethyl]indoline-2,3-dione]
(C16H22N2O2 274.36)
[4-[2-(Dipropylamino)ethyl]indoline-2,3-dione]
(C16H22N2O2 274.36)
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 4587
Pharmacopeial Forum: Volume No. 36(3) Page 678