Methadone Hydrochloride Injection

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 Injection is a sterile solution of Methadone Hydrochloride in Water for Injection. It contains, in each mL, NLT 9.5 mg and NMT 10.5 mg of methadone hydrochloride (C₂₁H₂₇NO.HCl). 

2 IDENTIFICATION 

Identification—Organic Nitrogenous Bases 〈181〉: Meets the requirements 

3 ASSAY 

Change to read: 

Procedure 

Internal standard solution: 5 mg/mL of procaine in methylene chloride 

Standard solution: Transfer 10 mg of USP Methadone Hydrochloride RS to a 60-mL separator. Add 1 mL of water and 2 mL of 0.5 N sodium hydroxide, and extract with three 10-mL portions of methylene chloride, combining the extracts in a vessel containing about 3 g of anhydrous sodium sulfate. Transfer 2.0 mL of Internal standard solution to the vessel containing the extracts, insert the stopper, and mix. 

Decant 15 mL of the methylene chloride solution to a test tube, and evaporate to a volume of 2–3 mL using vacuum or a stream of nitrogen. Sample solution: Transfer 1.0 mL of Injection, equivalent to 10 mg of methadone hydrochloride, to a 60-mL separator. Add 2 mL of 0.5 N sodium hydroxide, and extract with three 10-mL portions of methylene chloride, combining the extracts in a vessel containing about 3 g of anhydrous sodium sulfate. Transfer 2.0 mL of Internal standard solution to the vessel containing the extracts, insert the stopper, and mix. Decant 15 mL of the methylene chloride solution to a test tube, and evaporate to a volume of 2–3 mL using vacuum or a stream of nitrogen. Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: GC 

Detector: Flame ionization 

Column: Glass column, 1.2-m long and 4-mm in diameter; packed with 3% phase G2 on 100- to 200-mesh support S1A Temperatures 

Column: 170° 

Injection port: 225° 

Detector: 240° 

Carrier gas: Dry helium 

Flow rate: 55 mL/min 

Injection volume: Containing 5 µg of methadone 

System suitability 

Sample: Standard solution (six replicate injections) 

Suitability requirements 

Resolution: NLT 5.0 between methadone and procaine 

Coefficient of variation: NMT 1% in the ratios of the peak areas of methadone to the peak area of procaine 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the quantity, in mg, of methadone hydrochloride (C₂₁H₂₇NO. HCl) in each mL of Injection taken: 

Result = (R_U/R_S) × W

R_U = peak area ratio of methadone to procaine from the Sample solution 

R_S = peak area ratio of methadone to procaine from the Standard solution 

W = weight, in mg, of USP Methadone Hydrochloride RS in the Standard solution 

Acceptance criteria: 9.5–10.5 mg/mL 

4 SPECIFIC TESTS 

pH 〈791〉: 3.0–6.5 

Bacterial Endotoxins Test 〈85〉: NMT 8.8 USP Endotoxin Units/mg of methadone hydrochloride 

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉. 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in single-dose or multiple-dose, light-resistant containers, preferably of Type I glass. Change to read: 

USP Reference Standards 〈11〉 

USP Methadone Hydrochloride RS