Ropinirole Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Ropinirole Tablets contain ropinirole hydrochloride equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of ropinirole free base (C₁₆H₂₄N₂O).

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.

Add the following:

▲B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲ (USP 1-Dec-2019)

3 ASSAY

Change to read:

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 ropinirole in Buffer ▲(USP 1-Dec-2019) prepared as follows.▲

Transfer NLT 5 Tablets into a suitable volumetric flask and ▲(USP 1-Dec-2019) 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. ▲For Identification B, use a diode array detector in the range of 200–400 nm.▲ (USP 1-Dec-2019)

Column: 4.6-mm × 25-cm; 5-µm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: ▲NLT▲ (USP 1-Dec-2019) 2 times the retention time of ropinirole

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 the labeled amount of ropinirole (C₁₆H₂₄N₂O) in the portion of Tablets taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (Mᵤ / Mₛ) × 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)

Mᵤ = molecular weight of ropinirole, 260.37

Mₛ = molecular weight of ropinirole hydrochloride, 296.84

Acceptance criteria: 90.0%–110.0% of ropinirole free base

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

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: ▲0.0045 mg/mL▲ (USP 1-Dec-2019) of USP Ropinirole Hydrochloride RS in Medium

Sample solution: Pass a portion through a 0.45-µm filter, discard 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: 50 µL

Run time: ▲NLT▲ (USP 1-Dec-2019) 3× retention time of ropinirole

System suitability

Sample: Standard solution

Tailing factor: NMT 2.0

RSD: NMT 2.0%

Analysis

Result = (rᵤ / rₛ) × (Cₛ / L) × D × (Mᵤ / Mₛ) × V × 100

rᵤ = Sample peak

rₛ = Standard peak

Cₛ = concentration of USP Ropinirole HCl RS in Standard solution (mg/mL)

L = label claim (mg/Tablet)

D = dilution factor

Mᵤ = 260.37

Mₛ = 296.84

V = 500 mL

Tolerance: NLT 85% (Q)

Test 2

If product complies with this test, label indicates it meets USP Dissolution Test 2.

Medium: Citric acid 2.1 g/L, adjust with 121.2 g/L tris(hydroxymethyl)methylamine to pH 4.0; 500 mL (deaerated)

Apparatus 1: 50 rpm

Time: 15 min

Standard solution: (L/500) mg/mL in Medium

Buffer & mobile phase: as in Assay.

Sample solution: Filter through suitable 15–20 µm filter; discard first few mL. ▲[A polyethylene filter may be suitable.]▲ (USP 1-Dec-2019)

Chromatographic system

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Flow: ▲1 mL/min▲ (USP 1-Dec-2019)

Injection:

200 µL for 0.25, 0.5, 1.0, 2.0-mg Tablets

100 µL for others

Run time: ▲NLT 1.3× retention time▲ (USP 1-Dec-2019)

System suitability

Sample: Standard solution

RSD: NMT 1.5%

Analysis

Result = (rᵤ / rₛ) × (Cₛ / L) × (Mᵤ / Mₛ) × V × 100

Tolerance: NLT 80% (Q)

Uniformity of Dosage Units 〈905〉

Meet the requirements

IMPURITIES

Change to read:

Organic Impurities

Buffer: 1.8 g/L dibasic potassium phosphate; adjust to pH 7.4

Solution A: Methanol/Buffer (20:80)

Solution B: Methanol/Buffer (80:20)

Diluent: 5 g sodium dodecyl sulfate in 800 mL water → adjust to pH 6.8 → add 200 mL methanol.

Mobile phase: Table 1

System suitability solution: 0.3 µg/mL Ropinirole HCl RS + 0.5 µg/mL Ropinirole Related Compound B RS

Standard solution: 0.2 µg/mL ropinirole in Diluent

Sample solution: 100 µg/mL from ▲NLT 20 Tablets▲ (USP 1-Dec-2019), powdered → add 70% Diluent → shake 30 min → dilute → filter 0.45 µm

Chromatographic system

Mode: LC

Detector: UV 250 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temp: 50°

Flow: 1 mL/min

Injection: 100 µL

System suitability

Ropinirole vs compound B: Resolution NLT 2.0

Tailing factor: NMT 2.0

RSD: NMT 5.0%

Analysis

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (1/F) × 100

Acceptance criteria: Table 2

ᵃ 4-[2-(Propylamino)ethyl]indolin-2-one.

ᵇ N-[2-(2-Oxoindolin-4-yl)ethyl]-N-propylpropan-1-amine oxide.

ᶜ 1,2a,3,4-Tetrahydro-2H-cyclopenta(cd)indol-2-one.

ᵈ 4-[2-(Dipropylamino)ethyl]-1-hydroxy-1,3-dihydro-2H-indol-2-one.

ᵉ 4-[2-(Dipropylamino)ethyl]-1-ethyl-1,3-dihydro-2H-indol-2-one (process impurity for identification only).

ᶠ (Z)-4-[2-(Dipropylamino)ethyl]-3-propylideneindolin-2-one.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers; store at controlled room temperature.

Labeling: When more than one Dissolution test is given, labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Ropinirole Hydrochloride RS

USP Ropinirole Related Compound B RS

4-[2-(Dipropylamino)ethyl]indoline-2,3-dione hydrochloride

C₁₆H₂₂N₂O₂ · HCl 310.82