Medium: water;900mL.

Apparatus 2: 50rpm.

Time: 30minutes.

Mobile phaseand Chromatographic system— Prepare as directed in the Assay.

Standard preparation— Prepare a solution in methanol having known concentrations of about 0.02Amg of USP Acetaminophen RSper mL,0.02Bmg of USP Butalbital RSper mL,and 0.02Cmg of USP Caffeine RSper mL,in which A,B,and Care the labeled amounts,in mg,of acetaminophen,butalbital,and caffeine,respectively,per Tablet.Transfer 5.0mLof this solution to a 100-mLvolumetric 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 20µL)of the filtrate and the Standard preparationinto 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 Cis the concentration,in mg per mL,of the appropriate USP Reference Standard in the Standard preparation;and rUand rSare 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 C8H10N4O2is dissolved in 30minutes.

Mobile phase— Transfer 800mg of monobasic potassium phosphate to a 2000-mLvolumetric flask.Dissolve in 1100mLof 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 Suitabilityunder Chromatography á621ñ).

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

Butalbital standard stock solution— Dissolve an accurately weighed quantity of USP Butalbital RSin Internal standard solutionto obtain a solution having a known concentration of about 0.01Bmg per mL,Bbeing 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 RSin Internal standard solutionto obtain a solution having a known concentration of about 0.01Cmg per mL,Cbeing 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-mLvolumetric flask about 0.1Amg of USP Acetaminophen RS,Abeing the labeled amount,in mg,of acetaminophen per Tablet,10.0mLof Butalbital standard stock solution,and 10.0mLof Caffeine standard stock solution,sonicate for 5minutes,dilute with water to volume,and mix.This solution contains about 0.002Bmg of butalbital,0.002Amg of acetaminophen,and 0.002Cmg 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 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 1average Tablet weight,to a 200-mLvolumetric flask,add Internal standard solutionto volume,and mix.Sonicate for 15minutes,mix,and allow to cool and settle.Transfer 20.0mLof the clear supernatant to a 50-mLvolumetric 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 5mLof the filtrate.Use the clear filtrate as the Assay preparation.

Chromatographic system(see Chromatography á621ñ)— 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 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.16for acetaminophen,0.33for caffeine,0.77for phenacetin,and 1.0for 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 1000theoretical 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 10µL)of the Standard preparationand the Assay preparationinto 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 Dis the concentration,in mg per mL,of the appropriate USP Reference Standard in the Standard preparation;and RUand RSare the peak response ratios of the corresponding analyte to phenacetin obtained from the Assay preparationand the Standard preparation,respectively.