Medium: water; 900 mL.

Apparatus 2: 50 rpm.

Time: 30 minutes.

Mobile phase and Chromatographic system— Prepare as directed in the Assay.

Standard preparation— Prepare a solution in methanol having known concentrations of about 0.02A mg of USP Acetaminophen RS per mL, 0.02B mg of USP Butalbital RS per mL, and 0.02C mg of USP Caffeine RS per mL, in which A, B, and C are the labeled amounts, in mg, of acetaminophen, butalbital, and caffeine, respectively, per Tablet. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with water to volume, and mix.

Procedure— Pass a portion of the solution under test through a suitable filter having a 10-µm or finer porosity. Separately inject equal volumes (about 20 µL) of the filtrate and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantities, in mg, of butalbital (C11H16N2O3), acetaminophen (C8H9NO2), and caffeine (C8H10N4O2) dissolved by the same formula: 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 corresponding analyte obtained from the solution under test and the Standard preparation, respectively.

Tolerances— Not less than 80% (Q) of the labeled amounts of C11H16N2O3, C8H9NO2, and C8H10N4O2 is dissolved in 30 minutes.

(Official January 1, 2007)

Mobile phase— Transfer 800 mg of monobasic potassium phosphate to a 2000-mL volumetric flask. Dissolve in 1100 mL of water, dilute with methanol to volume, and mix. Pass through a suitable filter having a 0.5-µm or finer porosity. Make adjustments if necessary (see System Suitability under Chromatography 621).

Internal standard solution— Prepare a solution of phenacetin in methanol containing 0.65 mg per mL.

Butalbital standard stock solution— Dissolve an accurately weighed quantity of USP Butalbital RS in Internal standard solution to obtain a solution having a known concentration of about 0.01B mg per mL, B being the labeled amount, in mg, of butalbital per Tablet, sonicating and shaking the solution, if necessary, to achieve complete dissolution.

Caffeine standard stock solution— Dissolve an accurately weighed quantity of USP Caffeine RS in Internal standard solution to obtain a solution having a known concentration of about 0.01C mg per mL, C being the labeled amount, in mg, of caffeine per Tablet, sonicating and shaking the solution, if necessary, to achieve complete dissolution.

Standard preparation— Transfer to a 50-mL volumetric flask about 0.1A mg of USP Acetaminophen RS, A being the labeled amount, in mg, of acetaminophen per Tablet, 10.0 mL of Butalbital standard stock solution, and 10.0 mL of Caffeine standard stock solution, sonicate for 5 minutes, dilute with water to volume, and mix. This solution contains about 0.002B mg of butalbital, 0.002A mg of acetaminophen, and 0.002C mg of caffeine per mL. Pass a portion of this solution through a suitable filter having a 0.5-µm or finer porosity, and use the filtrate as the Standard preparation.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 1 average Tablet weight, to a 200-mL volumetric flask, add Internal standard solution to volume, and mix. Sonicate for 15 minutes, mix, and allow to cool and settle. Transfer 20.0 mL of the clear supernatant to a 50-mL volumetric flask, dilute with water to volume, and mix. Pass a portion of this solution through a suitable filter having a 0.5-µm or finer porosity, discarding the first 5 mL of the filtrate. Use the clear filtrate as the Assay preparation.

Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 216-nm detector and a 4-mm × 25-cm column that contains packing L1. 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 0.16 for acetaminophen, 0.33 for caffeine, 0.77 for phenacetin, and 1.0 for butalbital; the resolution, R, between any two peaks is not less than 1.2; the column efficiency, calculated from the butalbital peak, is not less than 1000 theoretical plates; and the relative standard deviations of the acetaminophen, caffeine, and butalbital responses for replicate injections are 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, and measure the peak responses for the major peaks. Calculate the quantities, in mg, of butalbital (C11H16N2O3), acetaminophen (C8H9NO2), and caffeine (C8H10N4O2) in the portion of Tablets taken by the same formula: in which D is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and RU and RS are the peak response ratios of the corresponding analyte to phenacetin obtained from the Assay preparation and the Standard preparation, respectively.