Medium: water;900mL.

Apparatus 1: 100rpm.

Time: 60minutes.

Determination of dissolved butalbital—

Mobile phase —Prepare a suitable filtered and degassed mixture of water,acetonitrile,and phosphoric acid (3100:725:4).Adjust the ratio as necessary.

Standard preparation —Dissolve accurately weighed quantities of USP Butalbital RSand of salicylic acid in Mobile phaseto obtain a solution containing known concentrations of about 1µg of butalbital per mLfor each mg of the labeled amount per Tablet and about 30µg of salicylic acid per mL.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 214-nm detector and a 3.9-mm ×30-cm column that contains 10-µm packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Standard preparationand record the peak responses as directed for Procedure:the resolution,R,between the butalbital and salicylic acid peaks is not less than 3.0;and the relative standard deviation of butalbital responses for replicate injections is not more than 3.0%.

Procedure —Filter a portion of the solution under test through a 0.5-µm filter.Separately inject equal volumes (about 10to 25µL)of the filtrate and the Standard preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.6for aspirin,0.85for salicylic acid,and 1.0for butalbital.[NOTE—After use,the column may be regenerated by passing through it at least 50mLof a mixture of acetonitrile,methanol,and water (1:1:1),followed by 50mLof a mixture of acetonitrile and water (1:1).]Calculate the amount,in mg,of butalbital (C11H16N2O3)dissolved by the formula: in which Cis the concentration,in µg per mL,of USP Butalbital RSin the Standard preparation;and rUand rSare the butalbital peak responses obtained from the solution under test and the Standard preparation,respectively.

Determination of dissolved aspirin—

Tolerances— Not less than 75%(Q)of the labeled amounts of butalbital (C11H16N2O3)and aspirin (C9H8O4)are dissolved in 60minutes.

Mobile phase— Prepare a suitable filtered and degassed mixture of water,acetonitrile,and phosphoric acid (3100:725:4).Adjust the ratio as necessary.

Solvent mixture— Mix 40mLof formic acid and 4000mLof acetonitrile.

Butalbital standard stock solution— Dissolve an accurately weighed quantity of USP Butalbital RSin Solvent mixtureto obtain a solution having a known concentration of about 3250Jµg per mL,Jbeing the ratio of the labeled amount,in mg,of butalbital to the labeled amount,in mg,of aspirin per tablet.

Salicylic acid standard stock solution— Dissolve an accurately weighed quantity of USP Salicylic Acid RSin Solvent mixtureto obtain a solution having a known concentration of about 200µg per mL.

Butalbital and salicylic acid standard preparation— Transfer 25.0mLof Butalbital standard stock solutionand 3.0mLof Salicylic acid standard stock solutionto a 250-mLvolumetric flask,dilute with Solvent mixtureto volume,and mix.This solution contains about 325Jµg of butalbital and 2.4µg of salicylic acid per mL.

Aspirin standard preparation— Dissolve an accurately weighed quantity of USP Aspirin RSin Solvent mixtureto obtain a solution having a known concentration of about 325µg per mL.

Resolution solution— Transfer 4.0mLof Butalbital standard stock solutionand 3.0mLof Salicylic acid standard stock solutionto a 50-mLvolumetric flask,dilute with Solvent mixtureto volume,and mix.

Assay preparation— Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 80mg of aspirin,to a 250-mLvolumetric flask,dilute with Solvent mixtureto volume,sonicate for 15minutes,and mix.Pass a portion of this solution through a 0.5-µm porosity filter before use.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 214-nm detector and a 3.9-mm ×30-cm column that contains 10-µm packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Butalbital and salicylic acid standard preparation,the Aspirin standard preparation,and the Resolution solutionas directed for Procedure:the resolution,R,between the butalbital and salicylic acid peaks is not less than 3.0;and the relative standard deviation for replicate injections of the Standard preparations is not more than 3.0%for butalbital and aspirin,and not more than 6.0%for salicylic acid.

Procedure— Separately inject equal volumes (about 10µL)of the Standard preparationsand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks,and for the minor peak corresponding to salicylic acid.The relative retention times are about 0.6for aspirin,0.85for salicylic acid,and 1.0for butalbital.[NOTE—After use,the column may be regenerated by passing through it at least 50mLof a mixture of acetonitrile,methanol,and water (1:1:1),followed by a mixture of acetonitrile and water (1:1).]Calculate the quantity,in mg,of butalbital (C11H16N2O3)in the portion of Tablets taken by the formula: in which Cis the concentration,in µg per mL,of USP Butalbital RSin the Butalbital and salicylic acid standard preparation;and rUand rSare the butalbital peak responses obtained from the Assay preparationand the Butalbital and salicylic acid standard preparation,respectively.Calculate the quantity,in mg,of aspirin (C9H8O4)in the portion of Tablets taken by the formula: in which Cis the concentration,in µg per mL,of USP Aspirin RSin the Aspirin standard preparation;and rUand rSare the aspirin peak responses obtained from the Assay preparationand the Aspirin standard preparation,respectively.Calculate the percentage of free salicylic acid in the Tablets taken by the formula: in which Cis the concentration,in µg per mL,of the USP Salicylic Acid RSin the Butalbital and salicylic acid standard preparation;ais the quantity,in mg,of aspirin in the portion of Tablets taken,based on the labeled amount;and rUand rSare the salicylic acid peak responses obtained from the Assay preparationand the Butalbital and salicylic acid standard preparation,respectively:not more than 3.0%is found.