Oxycodone and Acetaminophen Capsules
» Oxycodone and Acetaminophen Capsules contain Oxycodone Hydrochloride and Acetaminophen, or Oxycodone Hydrochloride, Oxycodone Terephthalate, and Acetaminophen. Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of oxycodone hydrochloride or oxycodone hydrochloride and oxycodone terephthalate, calculated as total oxycodone (C18H21NO4), and not less than 90.0 percent and not more than 110.0 percent of the labeled amount of acetaminophen (C8H9NO2).
Packaging and storage Preserve in tight, light-resistant containers.
USP Reference standards 11
A: To a quantity of Capsule contents, equivalent to about 2.5 mg of oxycodone, add 5 mL of a mixture of methanol and water (4:1), sonicate for 5 minutes, and shake by mechanical means for 15 minutes. Allow to settle, and use the clear supernatant as the test solution. Prepare a Standard solution of USP Oxycodone RS in the mixture of methanol and water (4:1) containing 0.5 mg per mL, and a second Standard solution of USP Acetaminophen RS in the same solvent containing 0.5J mg per mL, J being the ratio of the labeled amount, in mg, of acetaminophen to the labeled amount, in mg, of oxycodone per Capsule. Apply separate 20-µL portions of the test solution and the Standard solutions to a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of silica gel mixture. Allow the spots to dry, and develop the chromatogram in a solvent system consisting of a mixture of butyl alcohol, water, and glacial acetic acid (4:2:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the plate to air-dry for about 30 minutes. Expose the plate to iodine vapors in a closed chamber, and locate the spots: the RF values of the principal spots obtained from the test solution correspond to those obtained from the respective Standard solutions.
B: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution, Procedure for a Pooled Sample 711
Medium: 0.1 N hydrochloric acid; 900 mL.
Apparatus 2: 50 rpm.
Time: 45 minutes.
Procedure Determine the amounts of oxycodone (C18H21NO4) and acetaminophen (C8H9NO2) dissolved, employing the procedure set forth in the Assay, making any necessary volumetric adjustments, including adjusting the solution under test to a pH of about 5.5 before injecting.
Tolerances Not less than 75% (Q) of the labeled amounts of C18H21NO4 and C8H9NO2 is dissolved in 45 minutes.
Uniformity of dosage units 905: meet the requirements for Content Uniformity with respect to oxycodone and for Weight Variation with respect to acetaminophen.
Solvent mixture Prepare a suitable mixture of 0.05 M dibasic potassium phosphate and methanol (9:1), and adjust with phosphoric acid to a pH of 4.0. Make adjustments if necessary (see System Suitability under Chromatography 621).
Mobile phase Add 950 mg of monobasic potassium phosphate to 1000 mL of water. Add 1 mL of phosphoric acid, and stir until dissolved. While stirring, add 1 mL of n-nonylamine, and stir until a clear solution is obtained. Adjust with potassium hydroxide TS to a pH of 4.9 ± 0.1. Mix 9 volumes of this solution with 1 volume of methanol. Make adjustments if necessary (see System Suitability under Chromatography 621).
Oxycodone standard stock solution Dissolve an accurately weighed quantity of USP Oxycodone RS in Solvent mixture to obtain a solution having a known concentration of about 0.075 mg per mL.
Standard preparation Transfer about 0.75J mg of USP Acetaminophen RS, accurately weighed, J being the ratio of the labeled amount, in mg, of acetaminophen to that of oxycodone equivalent, to a 25-mL volumetric flask, add about 10 mL of Solvent mixture, and mix to dissolve. Add 10.0 mL of Oxycodone standard stock solution, dilute with Solvent mixture to volume, and mix. Transfer 5.0 mL of the solution so obtained to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 0.003 mg of USP Oxycodone RS and 0.003J mg of USP Acetaminophen RS per mL.
Assay preparation Weigh the contents of not fewer than 20 Capsules. Mix the contents, and transfer an accurately weighed portion of the powder, equivalent to about 4.5 mg of oxycodone, to a suitable container. Add 150.0 mL of Solvent mixture, and shake by mechanical means for 1 hour. Transfer 5.0 mL of the solution so obtained to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass the resulting solution through a membrane filter having a 0.5-µm or finer porosity, discarding the first 10 mL of the filtrate. Use the filtrate.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The column is maintained at a temperature of 40. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.6 for oxycodone and 1.0 for acetaminophen; the resolution, R, between acetaminophen and oxycodone is not less than 2.4; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of oxycodone (C18N21NO4) in the portion of Capsules taken by the formula:
1500C(rU / rS)in which C is the concentration, in mg per mL, of USP Oxycodone RS in the Standard preparation; and rU and rS are the oxycodone peak responses obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in the portion of Capsules taken by the formula:
1500C(rU / rS)in which C is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; and rU and rS are the acetaminophen peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 4175Pharmacopeial Forum: Volume No. 37(4)