Methadone Hydrochloride Tablets for Oral Suspension

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 

Methadone Hydrochloride Tablets for Oral Suspension contain NLT 93.0% and NMT 107.0% of the labeled amount of methadone hydrochloride (C₂₁H₂₇NO.HCl). 

2 IDENTIFICATION 

Thin-Layer Chromatographic Identification Test 〈201〉 

Sample solution: Shake a quantity of powdered Tablets for Oral Suspension equivalent to 5 mg of methadone hydrochloride with 5 mL of sodium carbonate TS, and extract with 5 mL of chloroform. 

Developing solvent system: Alcohol, glacial acetic acid, and water (5:3:2) 

Analysis: Proceed as directed, using iodoplatinate TS to visualize the spots. 

Acceptance criteria: Meet the requirements 

3 ASSAY

Procedure 

Mobile phase: Acetonitrile and 0.03 M monobasic potassium phosphate (40:60). Adjust with phosphoric acid to a pH of 3.2. Standard solution: 0.4 mg/mL of USP Methadone Hydrochloride RS in Mobile phase 

Sample solution: 0.4 mg/mL of methadone hydrochloride in Mobile phase. Prepare by transferring an amount of finely powdered Tablets for Oral Suspension (NLT 20) equivalent to 10 mg of methadone hydrochloride to a 25-mL volumetric flask, adding 10 mL of Mobile phase, and sonicating briefly. Shake by mechanical means for 15 min, dilute with Mobile phase to volume, and filter. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 30-cm; packing L11 

Flow rate: 1.5 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of methadone hydrochloride (C₂₁H₂₇NO.HCl) in the portion of Tablets for Oral Suspension taken: 

Result = (r_U/r_S) × (C_S/C_U) × L 

r_U = peak response from the Sample solution 

r_S = peak response from the Standard solution 

C_S = concentration of USP Methadone Hydrochloride RS in the Standard solution (mg/mL) 

C_U = nominal concentration of methadone hydrochloride in the Sample solution (mg/mL)Acceptance criteria: 93.0%–107.0% 

4 PERFORMANCE TESTS 

Disintegration 〈701〉 

Time: 15 min 

Acceptance criteria: Meet the requirements 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. 

Labeling: Label the Tablets for Oral Suspension to indicate that they are intended for dispersion in a liquid before oral administration of the prescribed dose. 

USP Reference Standards 〈11〉 

USP Methadone Hydrochloride RS