Ropinirole Hydrochloride

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 Hydrochloride contains NLT 98.0% and NMT 102.0% of ropinirole hydrochloride (C₁₆H₂₄N₂O · HCl), calculated on the anhydrous and solvent-free basis.

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.

Change to read:

C. Identification Tests—General 〈191〉, Chemical Identification Tests, Chloride

Sample: 20 mg/mL of Ropinirole Hydrochloride in water ▲(USP 1-May-2021)

Acceptance criteria: Meets the requirements ▲ (USP 1-May-2021)

3 ASSAY

Change to read:

Procedure

Buffer: 1.88 g of sodium 1-hexanesulfonate and 1 g of phosphoric acid in 1 L of water. Adjust with dilute triethylamine solution (1:10) to a pH of 6.5.

Diluent: Acetonitrile and water (20:80)

Mobile phase: Acetonitrile and Buffer (20:80)

Standard solution: 0.1 mg/mL of USP Ropinirole Hydrochloride RS in Diluent. Sonication may be used to aid dissolution.

Sample solution: 0.1 mg/mL of Ropinirole Hydrochloride in Diluent. Sonication may be used to aid dissolution.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

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

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT (USP 1-May-2021) 2.5 times the retention time of ropinirole

System suitability

Sample: Standard solution

Suitability requirements:

Tailing factor: NMT 1.6

Relative standard deviation: NMT 1.0% (USP 1-May-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of ropinirole hydrochloride (C₁₆H₂₄N₂O · HCl):

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of the Standard solution (mg/mL)

Cᵤ = concentration of the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0%, anhydrous and solvent-free basis.

4 IMPURITIES

Residue on Ignition 〈281〉

NMT 0.1%

Change to read: Limit of Palladium

[Note—Perform this test if Palladium is a known inorganic impurity.]

Solution A: Dissolve 2.4 g sodium hydroxide in 20 mL water and dilute with Glycerin (USP 1-May-2021) to 100 mL.

Solution B: 40 mg/mL thioacetamide in water.

Buffer: Carefully add 27 mL HCl to 25 g ammonium acetate; dilute to 100 mL.

Palladium standard solution: 10 ppm Pd (from ICP 1000 ppm stock).

Standard solution: Process as described; ignite, dissolve, filter (2 µm).

Sample solution: Carbonize 1 g sample; digest; filter (2 µm).

Analysis:

Add 1 mL Solution A, 0.2 mL Solution B, 2 mL Buffer → incubate 37° for 2 h → filter.

Acceptance criteria: Sample spot ≤ standard spot (10 ppm).

Organic Impurities — Procedure 1

Buffer, Diluent: As in Assay.

Solution A: Acetonitrile and Buffer (15:85)

Solution B: Acetonitrile and water (60:40)

Mobile phase: Table 1

System suitability solution: 1 mg/mL USP Ropinirole Hydrochloride RS + 1.5 µg/mL Ropinirole Related Compound B RS.

Sample solution: 1 mg/mL in Diluent.

Chromatographic system

Detector: UV 215 nm

Column: L7, 4.6-mm × 25-cm

Column temp: 30°

Flow: 1 mL/min

Injection: 10 µL

System suitability

Resolution: NLT 1.5 (ropinirole vs compound B)

Tailing factor: NMT 2.0

RSD: NMT 2.0%

Analysis

Result = (rᵤ / rₜ) × (1/F) × 100

rᵤ = peak of each impurity

rₜ = total peak area

F = relative response factor

Acceptance criteria: See Table 2.

ᵃ 2-{2-[2-(Dipropylamino)ethyl]-6-nitrophenyl}acetic acid

ᵇ 4-[2-(Propylamino)ethyl]indolin-2-one

ᶜ 4-[2-(Dipropylamino)ethyl]-1-hydroxyindolin-2-one

ᵈ Includes impurities ≥ 0.05%

Organic Impurities — Procedure 2

Solution A: 3.85 g/L ammonium acetate; adjust pH 2.5 with phosphoric acid

Solution B: Acetonitrile/methanol (70:30)

Diluent: A:B (84:16)

Mobile phase: Table 3

System suitability solution: 0.05 mg/mL each of Ropinirole Hydrochloride RS, Related Compound A RS, Related Compound B RS.

Standard solution: 3 µg/mL Related Compound B RS.

Sample solution: 1 mg/mL.

System suitability

Resolution:

NLT 2.0 (compound A vs compound B)

NLT 3.0 (compound B vs ropinirole)

Tailing factor: NMT 1.5

RSD: NMT 5.0% (compound B)

Analysis

Ropinirole Related Compound B

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

Other impurities:

Result = (rᵤ / rₜ) × 100

Acceptance criteria: See Table 4.

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

ᵇ For system suitability only

ᶜ 4-[2-(Dipropylamino)ethyl]-3-methyleneindolin-2-one

ᵈ 4-[2-(2-Methylpentylamino)ethyl]indolin-2-one

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

Organic Impurities — Procedure 3

Solution A: 3.95 g ammonium bicarbonate / 990 mL water + 4 mL 25% ammonia → dilute to 1 L (pH 9.2–9.3)

Solution B: Acetonitrile

Diluent: Acetonitrile/water (32:68)

Mobile phase: Table 5

Table 5

System suitability solution: 1 mg/mL Ropinirole HCl RS + 0.01 mg/mL Related Compound B RS

Standard solution: 1.2 µg/mL Ropinirole HCl RS

Sample solution: 1.2 mg/mL

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 3.9-mm × 15-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between ropinirole and ropinirole related compound B, System suitability solution

Tailing factor: 0.8–1.5 for ropinirole, Standard solution

Relative standard deviation: NMT 5.0% for ropinirole, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Ropinirole Hydrochloride taken:

Analysis

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

rᵤ = peak response ▲of each individual impurity▲ (USP 1-May-2021) from the Sample solution

rₛ= peak response ▲of ropinirole▲ (USP 1-May-2021) from the Standard solution

Cₛ = concentration of the Standard solution (mg/mL)

Cₛ = concentration of the Sample solution (mg/mL)

F = relative response factor (see Table 6)

Acceptance criteria: Table 6.

ᵃ 4-[2-(Dipropylamino)ethyl]-3-(hydroxyimino)indolin-2-one

ᵇ N,N-Dipropyl-N-(2-indol-4-ylethyl)amine

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I, Method Ic: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

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

Labeling: Label states Organic Impurities procedure used if not Procedure 1.

USP Reference Standards 〈11〉

USP Ropinirole Hydrochloride RS

USP Ropinirole Related Compound A RS

4-(2-Hydroxyethyl)indolin-2-one C₁₀H₁₁NO₂ 177.20

USP Ropinirole Related Compound B RS

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

C₁₆H₂₂N₂O₂ · HCl 310.82