Naltrexone 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)

DOWNLOAD PDF HERE

1 DEFINITION

Naltrexone Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of naltrexone hydrochloride (C₂₀H₂₃NO₄ · HCl).

2 IDENTIFICATION

Change to read:

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

3 ASSAY

Change to read:

3.1 Procedure

Solution A: Dissolve about 1.08 g of sodium 1-octanesulfonate and about 23.8 g of sodium acetate in 800 mL of water. Add 1.0 mL of triethylamine and 200 mL of methanol, and adjust with glacial acetic acid to a pH of 6.5 ± 0.1.

Solution B: Dissolve about 1.08 g of sodium 1-octanesulfonate and about 23.8 g of sodium acetate in 400 mL of water. Add 1.0 mL of triethylamine and 600 mL of methanol, and adjust with glacial acetic acid to a pH of 6.5 ± 0.1.

Mobile phase: See Table 1.

Table 1

Standard solution: 2.25 mg/mL of USP Naltrexone RS prepared as follows. Transfer an amount of USP Naltrexone RS to a suitable volumetric flask, add 15% of the final volume of methanol and 6% of the final volume of 0.1 N hydrochloric acid, and dissolve by swirling. Dilute with 0.1 M phosphoric acid to volume.

System suitability stock solution: 0.3 mg/mL of USP Naltrexone Related Compound A RS prepared as follows. Transfer a quantity of USP Naltrexone Related Compound A RS to a suitable volumetric flask, add 30% of the final volume of methanol, and dissolve by swirling. Dilute with 0.1 M phosphoric acid to volume.

System suitability solution: 1.125 mg/mL of USP Naltrexone RS and 0.015 mg/mL of USP Naltrexone Related Compound A RS prepared as follows. Transfer suitable volumes of System suitability stock solution and Standard solution to an adequate volumetric flask, and dilute with 0.1 M phosphoric acid to volume.

Sample solution: Nominally 2.5 mg/mL of naltrexone hydrochloride in 0.1 M phosphoric acid prepared as follows. Transfer NLT 20 Tablets to a tared container, and determine the average Tablet weight. Grind the Tablets to a homogeneous mixture. Transfer a portion of the powdered Tablets, equivalent to 250 mg of naltrexone hydrochloride, to a 100-mL volumetric flask. Add 80 mL of 0.1 M phosphoric acid and shake or sonicate for at least 30 min. Dilute with 0.1 M phosphoric acid to volume, mix, and filter.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 280 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 3.9-mm × 15-cm; 4-µm packing L1
• Flow rate: 1 mL/min
• Injection volume: 20 µL

System suitability

• Samples: Standard solution and System suitability solution 
• [Note-The relative retention times for naltrexone and naltrexone related compound A are 1.0 and 1.26, respectively.
• Suitability requirements
• Resolution: NLT 2.0 between naltrexone and naltrexone related compound A, System suitability solution
• Tailing factor: NMT 1.4, Standard solution
• Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naltrexone hydrochloride (C₂₀H₂₃NO₄ · HCl) in the portion of Tablets taken:

Result =(rᵤ/rₛ) × (Cₛ/Cᵤ) × (M_r₁/M_r₂) × 100

rᵤ = peak response of naltrexone from the Sample solution

rₛ = peak response of naltrexone from the Standard solution

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

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

M_r₁ = molecular weight of naltrexone hydrochloride, 377.86

M_r₂ = molecular weight of naltrexone, 341.41

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Change to read:

4.1 Dissolution 〈711〉

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 60 min

Standard solution: A known concentration of USP Naltrexone RS in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter.

Buffer: 0.05 M phosphate buffer (Dissolve 7.0 g of monobasic sodium phosphate in 1 L of water.)

Mobile phase: Mix 600 mL of Buffer, 1.1 g of sodium 1-octane sulfonate monohydrate, and 400 mL of methanol. Adjust with dilute sodium hydroxide to a pH of 6.7 ± 0.05.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 280 nm
• Column: 3.9-mm × 15-cm; packing L1
• Temperature: 45°
• Flow rate: 1 mL/min
• Injection volume: 100 µL

System suitability

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of naltrexone hydrochloride (C₂₀H₂₃NO₄ · HCl) dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × (M_r₁/M_r₂) × (1/L) × 100

rᵤ = peak response of naltrexone from the Sample solution

rₛ = peak response of naltrexone from the Standard solution

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

V = volume of Medium, 900 mL

M_r₁ = molecular weight of naltrexone hydrochloride, 377.86

M_r₂ = molecular weight of naltrexone, 341.41

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of naltrexone hydrochloride (C₂₀H₂₃NO₄ · HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Naltrexone RS

USP Naltrexone Related Compound A RS

17-(But-3-en-1-yl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride.

C₂₀H₂₃NO₄ · HCl    377.86