Methadone Hydrochloride Oral Solution
» Methadone Hydrochloride Oral Solution contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of methadone hydrochloride (C21H27NO·HCl).
Packaging and storage Preserve in tight containers, protected from light, at controlled room temperature.
USP Reference standards 11
A: Shake a volume of Oral Solution, equivalent to about 5 mg of methadone hydrochloride, with 5 mL of sodium carbonate TS, and extract with 5 mL of chloroform: the extract so obtained responds to the Thin-layer Chromatographic Identification Test 201, a solvent mixture of alcohol, glacial acetic acid, and water (5:3:2) being used for development and iodoplatinate TS being used to visualize the spots.
B: It responds to the tests for Chloride 191.
Uniformity of dosage units 905
for oral solution packaged in single-unit containers: meets the requirements.
Deliverable volume 698
for oral solution packaged in multiple-unit containers: meets the requirements.
pH 791: between 1.0 and 4.0.
Alcohol content, Method II 611 (if present): between 90.0% and 115.0% of the labeled amount of C2H5OH, determined by the gas-liquid chromatographic procedure, acetone being used as the internal standard.
Mobile phase Prepare a solution containing about 40 volumes of acetonitrile and 60 volumes of 0.033 M monobasic potassium phosphate adjusted, dropwise, with phosphoric acid to a pH of 4.0.
Internal standard solution Prepare a solution of pyrilamine maleate in water containing 250 µg per mL.
Standard preparation Transfer about 20 mg of USP Methadone Hydrochloride RS, accurately weighed, to a 25-mL volumetric flask, add 2.0 mL of Internal standard solution, dilute with water to volume, and mix.
Assay preparation Transfer an accurately measured volume of Oral Solution, equivalent to about 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, dilute with water to volume, and mix. Pass the solution through a 5-µm filter.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L11. The flow rate is about 1.3 mL per minute. Chromatograph five replicate injections of the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph by means of a suitable microsyringe or sampling valve, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 5.5 minutes for the internal standard and 9 minutes for methadone hydrochloride. Calculate the quantity, in mg, of methadone hyrdrochloride (C21H27NO·HCl) in each mL of the Oral Solution taken by the formula:
25(C/V)(RU / RS)in which C is the concentration, in mg per mL, of USP Methadone Hydrochloride RS in the Standard preparation; V is the volume, in mL, of Oral Solution taken; and RU and RS are the peak response ratios of the methadone hydrochloride to the internal standard peaks obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 3841Pharmacopeial Forum: Volume No. 30(1) Page 130