Methadone Hydrochloride Oral Concentrate

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 Concentrate contains, in each mL, NLT 9.0 mg and NMT 11.0 mg of methadone hydrochloride (C₂₁H₂₇NO.HCl). It contains a suitable preservative and may contain suitable coloring, flavoring, and surface-active agents. 

2 IDENTIFICATION 

Thin-Layer Chromatographic Identification Test 〈201〉 

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

Chromatographic system 

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 

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

3 ASSAY 

Procedure 

Mobile phase: Acetonitrile and 0.033 M monobasic potassium phosphate (40:60). Adjust with phosphoric acid to a pH of 4.0, filter, and degas. 

Standard solution: 0.4 mg/mL of USP Methadone Hydrochloride RS in Mobile phase 

Sample stock solution: Nominally 1 mg/mL of methadone hydrochloride from Oral Concentrate in Mobile phase 

Sample solution: 0.4 mg/mL of methadone hydrochloride in Mobile phase from Sample stock solution 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 3.9-mm × 30-cm; packing L11 

Flow rate: 2 mL/min 

Injection volume: 10 µL 

System suitability 

Sample: Standard solution 

Suitability requirements 

Column efficiency: NLT 1500 theoretical plates 

Tailing factor: NMT 2.0 

Relative standard deviation: NMT 2.0% for replicate injections 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the labeled amount of methadone hydrochloride (C₂₁H₂₇NO.HCl) in the portion of Oral Concentrate 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 the Sample solution (mg/mL) 

L = label claim (mg/mL) 

Acceptance criteria: 9.0–11.0 mg/mL 

4 SPECIFIC TESTS 

pH 〈791〉: 1.0–6.0 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight containers, protected from light, and store at controlled room temperature. Labeling: Label it to indicate that it is to be diluted with water or other liquid to 30 mL or more before administration. USP Reference Standards 〈11〉 

USP Methadone Hydrochloride RS