A: Dissolve 250 mg in 25 mL of water. Render the solution alkaline with 6 N ammonium hydroxide. Allow the mixture to stand until a precipitate is formed. Filter, wash the precipitate with 50 mL of cold water, and dry for 2 hours at 105: the precipitate so obtained melts between 218 and 223, but the range between beginning and end of melting does not exceed 2 (see Melting Range or Temperature 741).

B: Infrared Absorption 197K: using a portion of the dried precipitate obtained in Identification test A.

Test solution: 25 mg per mL, in water, calculated on the anhydrous, solvent-free basis.

Internal standard stock solution— Transfer 6.0 mL of isopropyl alcohol to a 500-mL volumetric flask, dilute with water to volume, and mix. [NOTE—The isopropyl alcohol must be free of alcohol impurities.]

Internal standard solution— Transfer 5.0 mL of Internal standard stock solution to a 100-mL volumetric flask, dilute with water to volume, and mix.

Standard solution— Prepare a solution of alcohol in water to obtain a solution having a known concentration of about 16 mg of alcohol (C2H5OH) per mL. Pipet 3.0 mL of this solution and 5.0 mL of the Internal standard stock solution into a 100-mL volumetric flask, dilute with water to volume, and mix.

Test solution— Transfer about 240 mg of Oxycodone Hydrochloride, accurately weighed, to a 15-mL centrifuge tube, add 5.0 mL of Internal standard solution, and mix to dissolve.

Chromatographic system (see Chromatography 621)— The gas chromatograph is equipped with a flame-ionization detector and a 4-mm × 1.8-m glass column that is packed with 80- to 100-mesh support S3, helium being used as the carrier gas. Prior to use, condition the column overnight at 235 with a slow flow of carrier gas. The column is maintained at 150, and the injection port and detector temperatures are maintained at 170. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the resolution, R, between isopropyl alcohol and alcohol is not less than 2; the tailing factor for alcohol is not more than 1.5; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure— Separately inject equal volumes (about 5 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of C2H5OH in the portion of Oxycodone Hydrochloride taken by the formula: in which CS is the concentration, in mg per mL, of alcohol (C2H5OH) in the Standard solution; CU is the concentration, in mg per mL, of oxycodone hydrochloride in the Test solution; and RU and RS are the ratios of the alcohol peak to the isopropyl alcohol peak obtained from the Test solution and the Standard solution, respectively. Not more than 1.0% (w/w) of alcohol (C2H5OH) is found.

100(ri / rs),

(Official January 1, 2007)

Mobile phase— Prepare a mixture of 0.005 M sodium 1-hexanesulfonate, methanol, phosphoric acid, and triethylamine (900:100:5:2). Adjust with 50% sodium hydroxide solution to a pH of 2.5 ± 0.1, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

Resolution solution— Prepare a solution in Mobile phase containing about 13 µg of codeine phosphate and 9 µg of oxycodone per mL.

Standard preparation— Quantitatively dissolve an accurately weighed quantity of USP Oxycodone RS in Mobile phase to obtain a solution having a known concentration of about 0.9 mg per mL.

Assay preparation— Transfer about 100 mg of Oxycodone Hydrochloride, accurately weighed, to a 100-mL volumetric flask, add about 50 mL of Mobile phase, and swirl to dissolve. Dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a filter having a 0.5-µm or finer porosity, and use the filtrate as the Assay preparation.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 206-nm detector and a 3.9-mm × 15-cm column that contains 4-µm packing L7 and is maintained at a constant temperature of about 50. The flow rate is about 1.5 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for codeine and 1.0 for oxycodone; and the resolution, R, between codeine and oxycodone is not less than 3.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is between 0.75 and 1.25; and the relative standard deviation for replicate injections 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, record the chromatograms for a period of time that is twice the retention time of the main oxycodone peak, and measure the responses for all the peaks. Calculate the quantity, in mg, of C18H21NO4·HCl in the portion of Oxycodone Hydrochloride taken by the formula: in which 351.82 and 315.37 are the molecular weights of oxycodone hydrochloride and oxycodone base, respectively; C is the concentration, in mg per mL, of USP Oxycodone RS in the Standard preparation; and rU and rS are the oxycodone peak area responses obtained from the Assay preparation and the Standard preparation, respectively.