Molindone Hydrochloride 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

Molindone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of molindone hydrochloride (C₁₆H₂₄N₂O₂ · HCl).

2 IDENTIFICATION

2.1 A. Thin-Layer Chromatography

Standard solution: 2.5 mg/mL of USP Molindone Hydrochloride RS in methanol

Sample solution: Nominally 2.5 mg/mL of molindone hydrochloride from finely powdered Tablets in methanol

Chromatographic system

• (See Chromatography 〈621〉, General Procedures, Thin-Layer Chromatography.)
• Adsorbent: 0.25-mm layer of chromatographic silica gel mixture
• Application volume: 5 µL
• Developing solvent system: Alcohol and 1 N hydrochloric acid (95:5)
• Spray reagent: Dragendorff's reagent, prepared as directed for technique 3 in Ordinary Impurities 〈466〉, Key for Visualization Techniques

Analysis

Samples: Standard solution and Sample solution

Proceed as directed in the chapter. Allow the spots to dry, protect the chromatogram from light, and develop in the Developing solvent system. Remove the plate from the developing chamber, mark the solvent front, and allow the solvent to evaporate. Locate the spots on the plate by spraying with Spray reagent.

Acceptance criteria: The Rf value of the principal spot from the Sample solution corresponds to that from the Standard solution.

3 ASSAY

3.1 Procedure

Mobile phase: Dissolve 1.1 g of sodium octanesulfonate in 480 mL of water. Add 520 mL of methanol, 2 mL of glacial acetic acid, and 0.4 mL of triethylamine. Pass through a filter of 0.45-µm pore size and degas.

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

Internal standard solution: 2 mg/mL of butylparaben prepared as follows. Transfer a suitable amount of butylparaben to a suitable volumetric flask, dissolve in methanol equivalent to 40% of the flask volume, and dilute with water to volume.

Standard solution: 0.5 mg/mL of USP Molindone Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Molindone Hydrochloride RS to a suitable volumetric flask, add Internal standard solution equivalent to 10% of the flask volume, and dilute with Diluent to volume.

Sample solution: Nominally 0.5 mg/mL of molindone hydrochloride from Tablets prepared as follows. Grind Tablets (NLT 20) to a homogeneous mixture, and transfer a portion equivalent to 50 mg of molindone hydrochloride to a 250-mL conical flask. Add 10.0 mL of Internal standard solution and 90.0 mL of Diluent, shake for 30 min, and filter.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 25-cm; packing L11
• Column temperature: 35°
• Flow rate: 1.5 mL/min
• Injection volume: 10 µL

System suitability

• Sample: Standard solution
• [Note-The relative retention times for molindone and butylparaben are about 0.7 and 1.0, respectively.]
• Suitability requirements
• Resolution: NLT 2 between molindone and butylparaben
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of molindone hydrochloride (C₁₆H₂₄N₂O₂ · HCl) in the portion of Tablets taken:

Result = (Rᵤ/Rₛ) × (Cₛ/Cᵤ) × 100

where:

Rᵤ = peak response ratio of molindone to butylparaben from the Sample solution

Rₛ = peak response ratio of molindone to butylparaben from the Standard solution

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

Cᵤ = nominal concentration of molindone hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 1: 100 rpm

Time: 30 min

Solution A: Methanol and 0.1 N hydrochloric acid (30:70)

Solution B: Methanol and 0.1 N hydrochloric acid (75:25)

Mobile phase: Dissolve 1.08 g of sodium 1-octanesulfonate in 480 mL of water. Add 520 mL of methanol, 2.0 mL of acetic acid, and 0.4 mL of triethylamine.

Standard solution: 2.4 µg/mL of USP Molindone Hydrochloride RS in Solution A

Sample solution: Withdraw a portion of the solution under test, and filter, discarding the first 3 mL of filtrate. Pipet 15.0 mL of this solution into a 25-mL volumetric flask and dilute with Solution B to volume.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 25-cm; packing L11
• Flow rate: 1.5 mL/min
• Injection volume: 100 µL

Analysis

Samples: Standard solution and Sample solution

Record the chromatograms, and measure the peak heights.

Calculate the percentage of the labeled amount of molindone hydrochloride (C₁₆H₂₄N₂O₂ · HCl) dissolved.

Tolerances: NLT 80% (Q) of the labeled amount of molindone hydrochloride (C₁₆H₂₄N₂O₂ · HCl) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Molindone Hydrochloride RS