Terpin Hydrate and Codeine Oral Solution (Monograph under this new title—to become official June 1,2005) (Current monograph title is Terpin Hydrate and Codeine Elixir) »Terpin Hydrate and Codeine Oral Solution contains,in each 100mL,not less than 1.53g and not more than 1.87g of terpin hydrate (C10H20O2·H2O),and not less than 180mg and not more than 220mg of codeine (C18H21NO3·H2O). Packaging and storage— Preserve in tight containers. USP Reference standards á11ñ 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 RSin methylene chloride to obtain a solution having a concentration of about 3mg per mL.[NOTE—Asmall volume of methanol may be used to aid dissolution of the terpin hydrate.] Standard solution B— Transfer 20mg of USP Codeine Phosphate RSto a suitable separator containing 10mLof water,add 1mLof 1Nsodium hydroxide,and mix.Add 10mLof methylene chloride,and shake for 1minute.Allow the layers to separate,and drain the lower organic layer into a suitable flask.Discard the aqueous layer. Test solution— Transfer 10mLof Oral Solution to a suitable separator containing 10mLof water,and add 1mLof 1Nsodium hydroxide.Add 10mLof methylene chloride,shake for 1minute,and allow the layers to separate.Use the clear lower organic layer as the Test solution. Procedure— Apply separately 5µLof Standard solution A,Standard solution B,and the Test solutionto a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture.Develop the chromatogram in a chromatographic chamber containing the Developing solventuntil 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 UVlight,and mark the location of the codeine spots.Spray the plate with phosphomolybdic acid TS,and heat at 105for 5minutes.The terpin hydrate spots appear blue on a yellow background.The RFvalues of the spots due to terpin hydrate and codeine obtained from the Test solutioncorrespond to those obtained from Standard solutions Aand B,respectively. Alcohol content,Method IIá611ñ: between 90.0%and 110.0%of the labeled amount of C2H5OH. Assay for terpin hydrate— Internal standard solution— Prepare a chloroform solution containing 20mg of biphenyl and 2.6mg of N-phenylcarbazole in each mL. Standard preparation— Transfer about 26mg of USP Codeine Phosphate RSand about 170mg of USP Terpin Hydrate RS,both accurately weighed,to a separator,add 5mLof alcohol,shake to dissolve the terpin hydrate,add 25mLof water to dissolve the codeine phosphate,add 10mLof 5Nsodium hydroxide,and extract with three 25-mLportions of chloroform,filtering each,successively,through cotton.Rinse the cotton with chloroform.To the combined rinse and extracts add 5.00mLof Internal standard solution,and mix. Assay preparation— Pipet 10mLof Oral Solution into a separator,add 20mLof water and 10mLof 5Nsodium hydroxide,and extract with three 25-mLportions of chloroform,filtering each,successively,through cotton.Rinse the cotton with chloroform.To the combined rinse and extracts add 5.00mLof Internal standard solution,and mix. Chromatographic system andSystem suitability— Proceed as directed in the Assayunder Terpin Hydrate.[NOTE—Heat the column to 230to remove the N-phenylcarbazole and codeine from prior injections.] Procedure— Inject about 1µLof the Standard preparationinto a suitable gas chromatograph,and record the chromatogram.Similarly,inject about 1µLof the Assay preparation,and record the chromatogram.Calculate the quantity,in mg,of terpin hydrate (C10H20O2·H2O)in each mLof the Oral Solution taken by the formula: 0.1(190.28/172.27)WS(RU/RS), in which 190.28and 172.27are the molecular weights of terpin hydrate (C10H20O2·H2O)and anhydrous terpin (C10H20O2);respectively,WSis the weight,in mg,of USP Terpin Hydrate RS,calculated on the anhydrous basis;and RUand RSare the area-ratios of terpin to biphenyl obtained from the chromatograms for the Assay preparationand the Standard preparation,respectively. Assay for codeine— Internal standard solution— Prepare as directed under Assay for terpin hydrate. Standard preparation— Evaporate the remaining Standard preparationfor Oral Solution from the Assay for terpin hydratenearly to dryness,and dissolve the residue in about 20mLof chloroform. Assay preparation— Evaporate the remaining Assay preparationfor Oral Solution from the Assay for terpin hydratenearly to dryness,and dissolve the residue in about 20mLof chloroform. Chromatographic system andSystem suitability— Proceed as directed in the Assayunder Terpin Hydrate,except to maintain the temperature of the column at 230instead of 120. Procedure— Proceed as directed under Assay for terpin hydrate,except to maintain the temperature of the column at 230instead of 120.The retention times for N-phenylcarbazole and codeine are about 7minutes and 10minutes,respectively.Calculate the quantity,in mg,of codeine (C18H21NO3·H2O)in each mLof the Oral Solution taken by the formula: 0.1(317.39/397.37)WS(RU/RS), in which 317.39and 397.37are the molecular weights of codeine (C18H21NO3·H2O)and codeine phosphate (C18H21NO3·H3PO4),respectively;WSis the weight,in mg,of USP Codeine Phosphate RS;and RUand RSare the area-ratios of codeine to N-phenylcarbazole obtained from the chromatograms for the Assay preparationand the Standard preparation,respectively. (Official June 1,2005) Auxiliary Information— Staff Liaison:Daniel K.Bempong,Ph.D.,Scientist Expert Committee:(PA2)Pharmaceutical Analysis 2 USP28–NF23Page 1873 Pharmacopeial Forum:Volume No.28(2)Page 375 Phone Number:1-301-816-8143