Terpin Hydrate and Codeine Oral Solution

» Terpin Hydrate and Codeine Oral Solution contains, in each 100 mL, not less than 1.53 g and not more than 1.87 g of terpin hydrate (C10H20O2·H2O), and not less than 180 mg and not more than 220 mg of codeine (C18H21NO3·H2O).

Packaging and storage— Preserve in tight containers.

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USP Terpin Hydrate RS

USP Codeine Phosphate RS

Identification—

Developing solvent— Prepare a mixture of methylene chloride and methanol (9:1).

Standard solution A— Dissolve a suitable quantity of USP Terpin Hydrate RS in methylene chloride to obtain a solution having a concentration of about 3 mg per mL. [note—A small volume of methanol may be used to aid dissolution of the terpin hydrate. ]

Standard solution B— Transfer 20 mg of USP Codeine Phosphate RS to a suitable separator containing 10 mL of water, add 1 mL of 1 N sodium hydroxide, and mix. Add 10 mL of methylene chloride, and shake for 1 minute. Allow the layers to separate, and drain the lower organic layer into a suitable flask. Discard the aqueous layer.

Test solution— Transfer 10 mL of Oral Solution to a suitable separator containing 10 mL of water, and add 1 mL of 1 N sodium hydroxide. Add 10 mL of methylene chloride, shake for 1 minute, and allow the layers to separate. Use the clear lower organic layer as the Test solution.

Procedure— Apply separately 5 µL of Standard solution A, Standard solution B, and the Test solution to a suitable thin-layer chromatographic plate (see Chromatography

621

) coated with a 0.25-mm layer of chromatographic silica gel mixture. Develop the chromatogram in a chromatographic chamber containing the Developing solvent until the solvent front has moved three-fourths of the length of the plate. Remove the plate from the chromatographic chamber, mark the solvent front, and allow the plate to dry. Examine the plate under short-wavelength UV light, and mark the location of the codeine spots. Spray the plate with phosphomolybdic acid TS, and heat at 105

for 5 minutes. The terpin hydrate spots appear blue on a yellow background. The RF values of the spots due to terpin hydrate and codeine obtained from the Test solution correspond to those obtained from Standard solutions A and B, respectively.

Alcohol content, Method II

611

: between 90.0% and 110.0% of the labeled amount of C2H5OH.

Assay for terpin hydrate—

Internal standard solution— Prepare a chloroform solution containing 20 mg of biphenyl and 2.6 mg of N-phenylcarbazole in each mL.

Standard preparation— Transfer about 26 mg of USP Codeine Phosphate RS and about 170 mg of USP Terpin Hydrate RS, both accurately weighed, to a separator, add 5 mL of alcohol, shake to dissolve the terpin hydrate, add 25 mL of water to dissolve the codeine phosphate, add 10 mL of 5 N sodium hydroxide, and extract with three 25-mL portions of chloroform, filtering each, successively, through cotton. Rinse the cotton with chloroform. To the combined rinse and extracts add 5.00 mL of Internal standard solution, and mix.

Assay preparation— Pipet 10 mL of Oral Solution into a separator, add 20 mL of water and 10 mL of 5 N sodium hydroxide, and extract with three 25-mL portions of chloroform, filtering each, successively, through cotton. Rinse the cotton with chloroform. To the combined rinse and extracts add 5.00 mL of Internal standard solution, and mix.

Chromatographic system and System suitability— Proceed as directed in the Assay under Terpin Hydrate. [note—Heat the column to 230

to remove the N-phenylcarbazole and codeine from prior injections. ]

Procedure— Inject about 1 µL of the Standard preparation into a suitable gas chromatograph, and record the chromatogram. Similarly, inject about 1 µL of the Assay preparation, and record the chromatogram. Calculate the quantity, in mg, of terpin hydrate (C10H20O2·H2O) in each mL of the Oral Solution taken by the formula:

0.1(190.28/172.27)WS(RU / RS)

in which 190.28 and 172.27 are the molecular weights of terpin hydrate (C10H20O2·H2O) and anhydrous terpin (C10H20O2); respectively, WS is the weight, in mg, of USP Terpin Hydrate RS, calculated on the anhydrous basis; and RU and RS are the area-ratios of terpin to biphenyl obtained from the chromatograms for the Assay preparation and the Standard preparation, respectively.

Assay for codeine—

Internal standard solution— Prepare as directed under Assay for terpin hydrate.

Standard preparation— Evaporate the remaining Standard preparation for Oral Solution from the Assay for terpin hydrate nearly to dryness, and dissolve the residue in about 20 mL of chloroform.

Assay preparation— Evaporate the remaining Assay preparation for Oral Solution from the Assay for terpin hydrate nearly to dryness, and dissolve the residue in about 20 mL of chloroform.

Chromatographic system and System suitability— Proceed as directed in the Assay under Terpin Hydrate, except to maintain the temperature of the column at 230

instead of 120

Procedure— Proceed as directed under Assay for terpin hydrate, except to maintain the temperature of the column at 230

instead of 120

. The retention times for N-phenylcarbazole and codeine are about 7 minutes and 10 minutes, respectively. Calculate the quantity, in mg, of codeine (C18H21NO3·H2O) in each mL of the Oral Solution taken by the formula:

0.1(317.39 / 397.37)WS(RU / RS)

in which 317.39 and 397.37 are the molecular weights of codeine (C18H21NO3·H2O) and codeine phosphate (C18H21NO3·H3PO4), respectively; WS is the weight, in mg, of USP Codeine Phosphate RS; and RU and RS are the area-ratios of codeine to N-phenylcarbazole obtained from the chromatograms for the Assay preparation and the Standard preparation, respectively.

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question	Contact	Expert Committee
Monograph	Clydewyn M. Anthony, Ph.D. Senior Scientific Liaison 1-301-816-8139	(SM22010) Monographs - Small Molecules 2
Reference Standards	RS Technical Services 1-301-816-8129 rstech@usp.org

USP35–NF30 Page 4797

Pharmacopeial Forum: Volume No. 28(2) Page 375