Methadone Hydrochloride Oral Solution

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 Oral Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of methadone hydrochloride (C₂₁H₂₇NO. HCl). 

2 IDENTIFICATION 

A. Thin-Layer Chromatographic Identification Test 〈201〉 

Sample solution: A volume of Oral Solution equivalent to 5 mg of methadone hydrochloride 

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

Analysis: Shake the Sample solution with 5 mL of sodium carbonate TS, and extract with 5 mL of chloroform. Proceed as directed using iodoplatinate TS to visualize the spots. 

Acceptance criteria: Meets the requirements 

B. Identification Tests—General, Chloride〈191〉: Meets the requirements 

3 ASSAY 

Procedure 

Mobile phase: Acetonitrile and 0.033 M monobasic potassium phosphate (40:60). Adjust dropwise with phosphoric acid to a pH of 4.0. Internal standard solution: 250 µg/mL of pyrilamine maleate 

Standard solution: Transfer 20 mg of USP Methadone Hydrochloride RS to a 25-mL volumetric flask. Add 2.0 mL of Internal standard solution, and dilute with water to volume. 

Sample solution: Transfer a volume of Oral Solution equivalent to 20 mg of methadone hydrochloride to a 125-mL separator. Extract the specimen with two 50-mL portions of ether, collecting the ether extracts in a second separator. Wash the combined ether extracts with 2 mL of water, and discard the ether extract. Transfer the aqueous wash and the aqueous specimen to a 25-mL volumetric flask. Add 2.0 mL of Internal standard solution, and dilute with water to volume. Pass the solution through a filter of 5-µm pore size. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 30-cm; packing L11 

Flow rate: 1.3 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

The retention times for the internal standard and methadone hydrochloride are about 5.5 and 9 min, respectively. 

Suitability requirements 

Relative standard deviation: NMT 2.0% 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of methadone hydrochloride (C₂₁H₂₇NO. HCl) in the Oral Solution taken: 

Result = (R_U/R_S) × (C_S/C_U) × 100 

R_U = peak response ratio of methadone hydrochloride to the internal standard from the Sample solution 

R_S = peak response ratio of methadone hydrochloride to the internal standard 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: 90.0%–110.0% 

4 OTHER COMPONENTS 

Alcohol Determination, Method II〈611〉(if present): 90.0%–115.0% of the labeled amount of C₂H₅OH, determined by the gas chromatographic procedure using acetone as the internal standard 

5 PERFORMANCE TESTS 

Uniformity of Dosage Units 〈905〉: Meets the requirements for Oral Solution packaged in single-unit containers 

Deliverable Volume 〈698〉: Meets the requirements for Oral Solution packaged in multiple-unit containers 

6 SPECIFIC TESTS 

pH 〈791〉: 1.0–4.0 

7 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, protected from light, and store at controlled room temperature. USP Reference Standards 〈11〉 

USP Methadone Hydrochloride RS