Molindone 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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C₁₆H₂₄N₂O₂ · HCl 312.84

4H-Indol-4-one, 3-ethyl-1,5,6,7-tetrahydro-2-methyl-5-(4-morpholinylmethyl)-, monohydrochloride;

3-Ethyl-6,7-dihydro-2-methyl-5-(morpholinomethyl)indol-4(5H)-one monohydrochloride CAS RN®: 15622-65-8  UNII: 1DWS68PNE6

1 DEFINITION

Molindone Hydrochloride contains NLT 98.0% and NMT 101.5% of molindone hydrochloride (C₁₆H₂₄N₂O₂ · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K. Do not dry the Standard or Sample.

Change to read:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. Identification Tests-General 〈191〉, Chemical Identification Tests, Chloride: Meets the requirements

3 ASSAY

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3.1 Procedure

Mobile phase: Dissolve 1.1 g of octanesulfonic acid sodium salt in 600 mL of water. Add 400 mL of methanol, 1 mL of glacial acetic acid, and 0.5 mL of triethylamine.

Diluent: Methanol and 0.01 N hydrochloric acid TS (40:60)

Standard solution: 0.5 mg/mL of USP Molindone Hydrochloride RS in Diluent

Sample solution: 0.5 mg/mL of Molindone Hydrochloride in Diluent

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L11
• Temperatures
• Autosampler: 4°
• Column: 35°
• Flow rate: 1.5 mL/min
• Injection volume: 5 µL
• Run time: NLT 1.7 times the retention time of molindone

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of molindone hydrochloride (C₁₆H₂₄N₂O₂ · HCl) in the portion of Molindone Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of molindone from the Sample solution

rₛ = peak response of molindone from the Standard solution

Cₛ = concentration of USP Molindone Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: 98.0%–101.5% on the anhydrous basis

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.25%

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4.2 Organic Impurities

Mobile phase and Diluent: Prepare as directed in the Assay.

System suitability solution: 2 mg/mL of USP Molindone Hydrochloride RS and 0.01 mg/mL of USP Molindone Related Compound A RS in Diluent

Sensitivity solution: 0.001 mg/mL of USP Molindone Hydrochloride RS in Diluent

Standard solution: 0.002 mg/mL each of USP Molindone Hydrochloride RS and USP Molindone Related Compound A RS in Diluent

Sample solution: 2 mg/mL of Molindone Hydrochloride in Diluent

Chromatographic system: Proceed as directed in the Assay, except for the Injection volume.

Injection volume: 20 µL

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

Suitability requirements

Resolution: NLT 5 between molindone and molindone related compound A, System suitability solution

Relative standard deviation: NMT 5.0% each of molindone and molindone related compound A, Standard solution

Signal-to-noise ratio: NLT 10 of molindone, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of molindone related compound A in the portion of Molindone Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of molindone related compound A from the Sample solution

rₛ = peak response of molindone related compound A from the Standard solution

Cₛ = concentration of USP Molindone Related Compound A RS in the Standard solution (mg/mL)

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

Calculate the percentage of any unspecified impurity in the portion of Molindone Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any unspecified impurity from the Sample solution

rₛ = peak response of molindone from the Standard solution

Cₛ = concentration of USP Molindone Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 1.

The reporting threshold is 0.05%.

Table 1

5 SPECIFIC TESTS

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5.1 pH 〈791〉

Sample solution: 10 mg/mL in water

Acceptance criteria: 4.0–5.0

5.2 Water Determination 〈921〉, Method I

NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers.

Change to read:

USP Reference Standards 〈11〉

USP Molindone Hydrochloride RS

USP Molindone Related Compound A RS

3-Ethyl-2-methyl-1,5,6,7-tetrahydro-4H-indol-4-one.

C₁₁H₁₅NO 177.25