Methadone Tablets

General Notices

Action and use

Opioid receptor agonist; analgesic.

Definition

Methadone Tablets contain Methadone Hydrochloride.

The tablets comply with the requirements stated under Tablets and with the following requirements.

Content of methadone hydrochloride, C21H27NO,HCl

92.5 to 107.5% of the stated amount.

Identification

A. Shake a quantity of the powdered tablets containing 0.1 g of Methadone Hydrochloride with 20 mL of water and centrifuge. Make the supernatant liquid alkaline with 5m sodium hydroxide, stir with a glass rod until the precipitate solidifies, filter, wash with water and dry over phosphorus pentoxide at room temperature at a pressure of 2 kPa. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of methadone (RS 218).
B. Extract a quantity of the powdered tablets containing 0.1 g of Methadone Hydrochloride with 10 mL of water, filter and wash the residue with sufficient water to bring the volume of the filtrate to 10 mL. Add to the filtrate 0.125 g of picrolonic acid dissolved in 50 mL of boiling water, stir and allow to stand for 2 hours. The melting point of the residue, after recrystallisation from ethanol (20%), washing with ethanol (20%) and drying at 105°, is about 160° or about 180°, Appendix V A.
C. Extract a quantity of the powdered tablets containing 5 mg of Methadone Hydrochloride with 5 mL of ethanol (96%), filter and evaporate the filtrate to dryness. To the residue add 0.05 mL of dinitrobenzene solution and 0.05 mL of a 50% w/v solution of sodium hydroxide. A purple colour is produced which changes slowly to dark brown.

Assay

Weigh and powder 20 tablets. To a quantity of the powder containing 50 mg of Methadone Hydrochloride add 60 mL of water and 5 mL of glacial acetic acid, heat on a water bath for 5 minutes, mix with the aid of ultrasound for 10 minutes and dilute to 100 mL with water. Filter through a glass fibre paper, discarding the first 10 mL of filtrate, and dilute 20 mL to 100 mL with water. To 10 mL of the resulting solution add 10 mL of phosphate buffer pH 4.9 and 5 mL of a 0.4% w/v solution of picric acid. Extract with three 15 mL quantities of chloroform and dilute the combined chloroform extracts to 50 mL with chloroform. To 10 mL add sufficient chloroform to produce 20 mL and measure the absorbance of the resulting solution, Appendix II B, at the maximum at 350 nm using in the reference cell a solution prepared in the same manner but using a 5% v/v solution of glacial acetic acid and beginning at the words ‘Filter through a glass fibre paper…’. Calculate the content of C21H27NO,HCl taking 448 as the value of A (1%, 1 cm) at the maximum at 350 nm.