Dissolution á711ñ—
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 (C
11H
16N
2O
3)dissolved by the formula:
0.9C(rU/rS),
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—
pH4.5Buffer—
Dissolve 5.98g of sodium acetate trihydrate in 500mLof water,add 2.5mLof glacial acetic acid,dilute with water to 1000mL,and mix.Adjust this solution with glacial acetic acid to a pHof 4.5±0.05,and mix.
Procedure
—Determine the amount of aspirin (C
9H
8O
4)dissolved from UVabsorbances at the wavelength of the isosbestic point of aspirin and salicylic acid at 265±2nm of filtered portions of the solution under test,diluted with 4volumes of
pH4.5Buffer,in comparison with a Standard solution having a known concentration of
USP Aspirin RSin the same medium.
[NOTE—Prepare the Standard solution at the time of use.An amount of alcohol not to exceed 1%of the total volume of the Standard solution may be used to bring the Reference Standard into solution prior to dilution first with water and then with 4volumes of
pH4.5Buffer.
]
Tolerances—
Not less than 75%(Q)of the labeled amounts of butalbital (C11H16N2O3)and aspirin (C9H8O4)are dissolved in 60minutes.
Assay for butalbital and aspirin and limit of free salicylic acid—
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 3250
Jµg 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 (C
11H
16N
2O
3)in the portion of Tablets taken by the formula:
0.25C(rU/rS),
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 (C
9H
8O
4)in the portion of Tablets taken by the formula:
0.25C(rU/rS),
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:
25(C/a)(rU/rS),
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.