A: Transfer 50mLof the filtrate retained from the test for Terephthalate acid contentto a 125-mLconical flask.Render the solution alkaline with 6Nammonium hydroxide.Allow the mixture to stand until a precipitate is formed.Filter,wash the precipitate with 50mLof cold water,and dry for 2hours at 105:the precipitate so obtained melts between 218and 223,but the range between beginning and end of melting does not exceed 2(see Melting Range or Temperature á741ñ).

B: Infrared Absorption á197Kñ:using a portion of the dried precipitate obtained in Identificationtest A,and the USP Oxycodone RS.

C:Ultraviolet Absorption á197Uñ—

Solution A— Dissolve 2.2g of sodium 1-octanesulfonate in 850mLof water,and add 150mLof methanol,20mLof glacial acetic acid,and 1.0mLof triethylamine.Mix,pass through a filter having a 0.5-µm or finer porosity,and degas.

Solution B— Dissolve 2.2g of sodium 1-octanesulfonate in 500mLof water,and add 500mLof methanol,20mLof glacial acetic acid,and 1.0mLof triethylamine.Mix,pass through a filter having a 0.5-µm or finer porosity,and degas.

Mobile phase— Use variable mixtures of Solution Aand Solution Bas directed for Chromatographic system.Make adjustments to either Solutionas necessary (see System Suitabilityunder Chromatography á621ñ).

Diluting solution— Use 0.1Nhydrochloric acid.

Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Oxycodone RSin Diluting solutionto obtain a stock standard solution having a known concentration of about 0.9mg per mL.Transfer 10.0mLof this stock standard solution to a 100-mLvolumetric flask,add 20mLof methanol,dilute with Diluting solutionto volume,and mix.

Resolution solution— Dissolve a quantity of 4-hydroxybenzoic acid isopropyl ester in methanol to obtain a solution having a concentration of about 0.05mg per mL.Transfer 20mLof this solution and 10mLof the stock standard solution used to prepare the Standard preparationto a 100-mLvolumetric flask,dilute with Diluting solutionto volume,and mix.

Test preparation— Transfer about 110mg of Oxycodone Terephthalate,accurately weighed,to a 10-mLvolumetric flask,add 8mLof methanol,and shake by mechanical means for about 20minutes to dissolve.Dilute with methanol to volume,and mix.

Chromatographic system(see Chromatography á621ñ)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm ×15-cm column that contains packing L1,is maintained at 45±1,and is programmed to provide variable mixtures of Mobile phase.The flow rate is about 1.5mLper minute.Equilibrate the system with a mobile phase consisting of a mixture of 90%Solution Aand 10%Solution B.After each injection of the Standard preparation,Resolution solution,and Test preparation,the composition of the mobile phase is changed linearly over the next 30minutes so that at the end of that time it consists of 80%Solution Aand 20%Solution B,and is then changed linearly over the next 20minutes so that at the end of that time it consists of 100%Solution B,which is then maintained for 5minutes.Chromatograph the Resolution solution,and record the peak responses as directed for Procedure:the resolution,R,between the oxycodone peak and the 4-hydroxybenzoic acid isopropyl ester peak is not less than 8.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 5.0%.

Procedure— Inject about 25µLof the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of each impurity in relation to the oxycodone component taken by the formula: in which 398.43is one-half of the molecular weight of oxycodone terephthalate;315.37is the molecular weight of oxycodone;Cis the concentration,in mg per mL,of USP Oxycodone RSin the Standard preparation;Mis the quantity,in mg,of Oxycodone Terephthalate taken to prepare the Test preparation;riis the area of an individual impurity peak obtained from the Test preparation;and rSis the area of the oxycodone peak obtained from the Standard preparation.If any impurity is found having a retention time of about 2in relation to that of the oxycodone peak,divide its apparent percentage by 4.8:no individual impurity exceeds 1.0%,and the sum of all impurities does not exceed 2.0%.

Mobile phase— Dissolve 2.2g of sodium 1-octanesulfonate in 740mLof water,add 260mLof methanol,10mLof glacial acetic acid,and 0.1mLof triethylamine.Mix,and adjust with 5Nsodium hydroxide to a pHof 6.5±0.1.Pass through a suitable filter having a 0.5-µm or finer porosity,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Diluting solution— Use 0.1Nhydrochloric acid.

Internal standard solution— Transfer about 50mg of ethylparaben to a 500-mLvolumetric flask,add 10mLof methanol,and swirl to dissolve.Dilute with Diluting solutionto volume,and mix.

Standard preparation— Dissolve an accurately weighed quantity of USP Oxycodone RSin Diluting solution,and quantitatively dilute with Diluting solutionto obtain a stock solution having a known concentration of about 0.75mg per mL.Transfer 15.0mLof this stock solution to a 100-mLvolumetric flask,add 20.0mLof Internal standard solution,dilute with Diluting solutionto volume,and mix to obtain a Standard preparationhaving a known concentration of about 0.1125mg of USP Oxycodone RSper mL.

Assay preparation— Transfer about 142mg of Oxycodone Terephthalate,accurately weighed,to a 200-mLvolumetric flask,dilute with Diluting solutionto volume,and mix.Filter this solution,discarding the first 5mLof the filtrate.Transfer 10.0mLof the clear filtrate to a 50-mLvolumetric flask,add 10.0mLof Internal standard solution,dilute with Diluting solutionto volume,and mix.Use this solution as the Assay preparation.

Chromatographic system (see Chromatography á621ñ)— The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm ×15-cm column that contains packing L1and is maintained at a temperature of 50±1.0.The flow rate is about 1mLper minute.Chromatograph the Standard preparation,and record the responses as directed for Procedure:the column efficiency,determined from the oxycodone peak,is not less than 1800theoretical plates;the resolution,R,between oxycodone and ethylparaben is not less than 6;and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 30µL)of the Standard preparation and the Assay preparation into the chromatograph,record the chromatograms for a period of time that is twice the retention time of the main oxycodone peak,and measure the peak responses for ethylparaben and oxycodone.Calculate the quantity,in mg,of (C18H21NO4)2·C8H6O4in the portion of Oxycodone Terephthalate taken by the formula: in which 398.43is one-half of the molecular weight of oxycodone terephthalate;315.37is the molecular weight of oxycodone;Cis the concentration,in mg per mL,of USP Oxycodone RSin the Standard preparation;and RUand RSare the ratios of the peak response of oxycodone to that of ethylparaben obtained from the Assay preparationand the Standard preparation,respectively.