Dissolution 
711
—
Medium:
water; 900 mL.
Apparatus 1:
100 rpm.
Time:
60 minutes.
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 RS and of salicylic acid in
Mobile phase to obtain a solution containing known concentrations of about 1 µg of butalbital per mL for each mg of the labeled amount per Tablet and about 30 µg of salicylic acid per mL.
Chromatographic system
(see
Chromatography 621)—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 1.5 mL per minute. Chromatograph the
Standard preparation and 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 10 to 25 µL) of the filtrate and the
Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.6 for aspirin, 0.85 for salicylic acid, and 1.0 for butalbital.
[NOTE—After use, the column may be regenerated by passing through it at least 50 mL of a mixture of acetonitrile, methanol, and water (1:1:1), followed by 50 mL of 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
C is the concentration, in µg per mL, of
USP Butalbital RS in the
Standard preparation; and
rU and
rS are the butalbital peak responses obtained from the solution under test and the
Standard preparation, respectively.
Determination of dissolved aspirin—
pH 4.5 Buffer—
Dissolve 5.98 g of sodium acetate trihydrate in 500 mL of water, add 2.5 mL of glacial acetic acid, dilute with water to 1000 mL, and mix. Adjust this solution with glacial acetic acid to a pH of 4.5 ± 0.05, and mix.
Procedure
—Determine the amount of aspirin (C
9H
8O
4) dissolved from UV absorbances at the wavelength of the isosbestic point of aspirin and salicylic acid at 265 ± 2 nm of filtered portions of the solution under test, diluted with 4 volumes of
pH 4.5 Buffer, in comparison with a Standard solution having a known concentration of
USP Aspirin RS in 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 4 volumes of
pH 4.5 Buffer.
]
Tolerances—
Not less than 75% (Q) of the labeled amounts of butalbital (C11H16N2O3) and aspirin (C9H8O4) are dissolved in 60 minutes.
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 40 mL of formic acid and 4000 mL of acetonitrile.
Butalbital standard stock solution—
Dissolve an accurately weighed quantity of
USP Butalbital RS in
Solvent mixture to obtain a solution having a known concentration of about 3250
J µg per mL,
J being 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 RS in
Solvent mixture to obtain a solution having a known concentration of about 200 µg per mL.
Butalbital and salicylic acid standard preparation—
Transfer 25.0 mL of Butalbital standard stock solution and 3.0 mL of Salicylic acid standard stock solution to a 250-mL volumetric flask, dilute with Solvent mixture to volume, and mix. This solution contains about 325J µg of butalbital and 2.4 µg of salicylic acid per mL.
Aspirin standard preparation—
Dissolve an accurately weighed quantity of
USP Aspirin RS in
Solvent mixture to obtain a solution having a known concentration of about 325 µg per mL.
Resolution solution—
Transfer 4.0 mL of Butalbital standard stock solution and 3.0 mL of Salicylic acid standard stock solution to a 50-mL volumetric flask, dilute with Solvent mixture to volume, and mix.
Assay preparation—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 80 mg of aspirin, to a 250-mL volumetric flask, dilute with Solvent mixture to volume, sonicate for 15 minutes, and mix. Pass a portion of this solution through a 0.5-µm porosity filter before use.
Chromatographic system
(see
Chromatography 621)—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 1.5 mL per minute. Chromatograph the
Butalbital and salicylic acid standard preparation, the
Aspirin standard preparation, and the
Resolution solution 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 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 10 µL) of the
Standard preparations and the
Assay preparation into 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 0.6 for aspirin, 0.85 for salicylic acid, and 1.0 for butalbital.
[NOTE—After use, the column may be regenerated by passing through it at least 50 mL of 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
C is the concentration, in µg per mL, of
USP Butalbital RS in the
Butalbital and salicylic acid standard preparation; and
rU and
rS are the butalbital peak responses obtained from the
Assay preparation and 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
C is the concentration, in µg per mL, of
USP Aspirin RS in the
Aspirin standard preparation; and
rU and
rS are the aspirin peak responses obtained from the
Assay preparation and 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
C is the concentration, in µg per mL, of the
USP Salicylic Acid RS in the
Butalbital and salicylic acid standard preparation; a is the quantity, in mg, of aspirin in the portion of Tablets taken, based on the labeled amount; and
rU and
rS are the salicylic acid peak responses obtained from the
Assay preparation and the
Butalbital and salicylic acid standard preparation, respectively: not more than 3.0% is found.
