Aspirin, Caffeine, and Dihydrocodeine Bitartrate Capsules

» Aspirin, Caffeine, and Dihydrocodeine Bitartrate Capsules contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of aspirin (C9H8O4), caffeine (C8H10N4O2), and dihydrocodeine bitartrate (C18H23NO3·C4H6O6).

Packaging and storage— Preserve in tight containers.

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USP Aspirin RS

USP Caffeine RS

USP Dihydrocodeine Bitartrate RS

USP Salicylic Acid RS

Identification— The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation obtained as directed in the Assay.

Dissolution, Procedure for a Pooled Sample

711

—

Medium: 0.05 M acetate buffer, prepared by mixing 2.99 g of sodium acetate trihydrate and 1.66 mL of glacial acetic acid with water to obtain 1000 mL of solution having a pH of 4.50 ± 0.05; 500 mL.

Apparatus 1: 50 rpm.

Time: 45 minutes.

Mobile phase and Chromatographic system—Prepare as directed in the Assay and limit of salicylic acid.

Standard preparation— Prepare a solution in Medium containing known concentrations of about 0.002A mg of USP Aspirin RS, 0.002C mg of USP Caffeine RS, and 0.002D mg of USP Dihydrocodeine Bitartrate RS per mL, A, C, and D being the labeled amounts, in mg, of aspirin, caffeine, and dihydrocodeine bitartrate, respectively, in each Capsule.

Test preparation— Filter a portion of the solution under test.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantities, in mg, of aspirin (C9H8O4), caffeine (C8H10N4O2), and dihydrocodeine bitartrate (C18H23NO3·C4H6O6) dissolved by the same formula:

500C(rU / rS)

in which C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and rU and rS are the peak responses of the relevant analyte obtained from the Test preparation and the Standard preparation, respectively.

Tolerances— Not less than 75% (Q) of the labeled amounts of C9H8O4, C8H10N4O2, and C18H23NO3·C4H6O6 are dissolved in 45 minutes.

Uniformity of dosage units

905

: meet the requirements.

Assay and limit of salicylic acid—

Mobile phase— Dissolve 1 g of sodium 1-pentanesulfonate and 2.3 g of monobasic ammonium phosphate in 850 mL of water. Add 150 mL of acetonitrile, mix, degas, and adjust with phosphoric acid to a pH of 2.5. Make adjustments if necessary (see System Suitability under Chromatography

621

Diluent— Prepare a mixture of water and acetonitrile (53:46), and adjust with phosphoric acid to a pH of 2.5.

Standard preparation— Prepare a solution in Diluent containing known concentrations of about 0.001A mg of USP Aspirin RS, 0.001C mg of USP Caffeine RS, and 0.001D mg of USP Dihydrocodeine Bitartrate RS per mL, A, C, and D being the labeled amounts, in mg, of aspirin, caffeine, and dihydrocodeine bitartrate, respectively, in each Capsule. [note—Use this solution within 3 hours. ]

Standard salicylic acid preparation— Dissolve an accurately weighed quantity of USP Salicylic Acid RS in Diluent to obtain a solution having a known concentration of about 0.005A µg per mL, A being the labeled amount, in mg, of aspirin per Capsule. [note—Use this solution within 3 hours. ]

Resolution solution— Prepare a solution in Standard preparation containing about 0.0001A mg of USP Salicylic Acid RS per mL, A being the labeled amount, in mg, of aspirin in each Capsule. [note—Use this solution within 3 hours. ]

Assay preparation— Transfer the contents of 10 Capsules to a 500-mL volumetric flask. Dilute with Diluent to volume, and mix. Transfer 5.0 mL of this mixture to a 100-mL volumetric flask, dilute with Diluent to volume, and mix. Centrifuge a portion of this mixture, and use the clear supernatant as the Assay preparation. [note—Use this solution within 3 hours. ]

Chromatographic system— The liquid chromatograph is equipped with a 215-nm detector and a 4.6-mm × 15-cm column that contains packing L7. The flow rate is about 2 mL per minute. Chromatograph the Resolution solution, and record the responses as directed for Procedure: the relative retention times are about 0.2 for caffeine, 0.3 for dihydrocodeine, 0.7 for aspirin, and 1.0 for salicylic acid; and the resolution, R, between the caffeine and dihydrocodeine peaks is not less than 2.5, between the dihydrocodeine and aspirin peaks is not less than 1.0, and between the aspirin and salicylic acid peaks is not less than 1.5. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0% for each analyte.

Procedure— Separately inject equal volumes (about 10 µL) of the Assay preparation, the Standard preparation, and the Standard salicylic acid preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantities, in mg, of aspirin (C9H8O4), caffeine (C8H10N4O2), and dihydrocodeine bitartrate (C18H23NO3·C4H6O6) in each Capsule taken by the same formula:

1000C(rU / rS)

in which C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and rU and rS are the responses of the corresponding analyte peaks of the Assay preparation and the Standard preparation, respectively. Calculate the percentage of salicylic acid in the Capsules taken by the formula:

100(C / A)(rU / rS)

in which C is the concentration, in µg per mL, of USP Salicylic Acid RS in the Standard salicylic acid preparation; A is the labeled amount, in mg, of aspirin in each Capsule taken; and rU and rS are the salicylic acid peak responses obtained from the Assay preparation and the Standard salicylic acid preparation, respectively: not more than 3.0% is found.

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
711	Margareth R.C. Marques, Ph.D. Senior Scientific Liaison 1-301-816-8106	(GCDF2010) General Chapters - Dosage Forms

USP35–NF30 Page 2255

Pharmacopeial Forum: Volume No. 30(1) Page 60