Chromatographic purity—
Solution A:
0.1% phosphoric acid adjusted with phosphoric acid to a pH of 2.00 ± 0.1.
Solution B—
Use acetonitrile.
Mobile phase—
Use variable mixtures of
Solution A and
Solution B as directed for
Chromatographic system. Make adjustments if necessary (see
System Suitability under
Chromatography 
621
).
Diluent A:
a mixture of acetonitrile, methylene chloride, and water (48:1:1).
Diluent B:
a mixture of acetonitrile and water (1:1).
Standard stock solution—
Dissolve an accurately weighed quantity of
USP Oxaprozin RS in acetonitrile to obtain a solution having a concentration of about 200 µg per mL.
Standard solution—
Transfer 5.0 mL of Standard stock solution to a 200-mL volumetric flask, and dilute with Diluent A to volume.
Benzil solution:
200 µg of benzil per mL in acetonitrile.
Resolution solution—
Transfer 5.0 mL of Benzil solution and 5.0 mL of Standard stock solution to a 100-mL volumetric flask, and dilute with Diluent A to volume to obtain a solution having known concentrations of about 10 µg of each per mL.
Test solution A—
[NOTE—Test solution A is used to monitor all known and unknown impurities, except imidazolic acid and oximide.] Transfer about 100 mg of Oxaprozin, accurately weighed, to a 100-mL volumetric flask; add 2 mL of methylene chloride, 2 mL of water, and 75 mL of acetonitrile; and sonicate after each solvent is added. Dilute with acetonitrile to volume.
Test solution B—
[NOTE—Test solution B is used to monitor only imidazolic acid and oximide.] Transfer about 100 mg of Oxaprozin, accurately weighed, to a 100-mL volumetric flask; add 75 mL of Diluent B to dissolve the Oxaprozin; and dilute with Diluent B to volume.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 238-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L7. The flow rate is 1.0 mL per minute. The chromatograph is programmed as follows.
Time
(minutes) |
Solution A
(%) |
Solution B
(%) |
Elution |
| 0 |
70 |
30 |
equilibration |
| 0–20 |
70 |
30 |
isocratic |
| 21–60 |
70®0 |
30®100 |
linear gradient |
| 60–61 |
0®70 |
100®30 |
linear gradient |
| 61–70 |
70 |
30 |
isocratic |
Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.1 for benzil and 1.0 for oxaprozin; and the resolution, R, between oxaprozin and benzil is not less than 3.0. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0, and the relative standard deviation for replicate injections is not more than 5.0 %.
Procedure—
Inject 20 µL of
Test solution A and
Test solution B into the chromatograph, record the chromatogram, and measure the areas for all the peaks. Calculate the percentage of each impurity in the portion of Oxaprozin taken by the formula:
100(Fri / rs),
in which
F is the relative response factor and is equal to 1.15 for the imidazolic acid peak with a relative retention time of 0.14, 1.21 for any peak with a relative retention time of 0.42, 0.91 for the oximide peak with a relative retention time of 0.73, 0.85 for any peak with a relative retention time of 0.84, 1.29 for any peak with a relative retention time of 1.08, 1.46 for any peak with a relative retention time of 1.50, and 2.09 for any peak with a relative retention time of 1.57;
ri is the peak response for each impurity; and
rs is the sum of the responses of all the peaks: not more than 0.1% of any individual impurity is found, and not more than 0.5% of total impurities is found.
[NOTE—The values of
F for all known impurities except imidazolic acid and oximide were found using
Test solution A, and the values of
F for imidazolic acid and oximide were found using
Test solution B.]
Assay—
Dissolve about 400 mg of Oxaprozin, previously dried at 105
for 2 hours and accurately weighed, in about 100 mL of alcohol in a narrow-mouth container, and titrate with 0.1 N sodium hydroxide VS, determining the endpoint potentiometrically (see
Titrimetry 541). Each mL of 0.1 N sodium hydroxide is equivalent to 29.332 mg of oxaprozin.
;)
