Heavy metals, Method II 
231
—
To prepare the
Test Preparation, use a 100-mL borosilicate glass beaker or a quartz crucible. If the residue is not completely white after the ignition at 500
to 600
, add enough hydrogen peroxide to dissolve it, heat gently until dry, and ignite for 1 hour. Repeat the hydrogen peroxide treatment and ignition until the residue is completely white. Proceed as directed in
Test Preparation, beginning with “Cool, add 4 mL of 6 N hydrochloric acid.” The limit is 0.001%.
Chromatographic purity—
pH 2.5 Phosphate buffer—
Mix equal volumes of 0.01 M phosphoric acid and 0.01 M monobasic sodium phosphate. If necessary, adjust with additional portions of the appropriate component to a pH of 2.5 ± 0.2.
Mobile phase—
Prepare a filtered and degassed mixture of methanol and
pH 2.5 Phosphate buffer (700:300). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
[NOTE—Increasing the proportion of buffer increases resolution.
]
Diluent—
Prepare a mixture of methanol and water (70:30).
Standard solution—
Prepare a solution of
USP Diclofenac Related Compound A RS in methanol having a known concentration of about 0.75 mg per mL. Quantitatively dilute an accurately measured volume of this stock solution with
Diluent to obtain a solution having a known concentration of about 1.5 µg per mL.
Test solution—
Transfer about 75 mg of Diclofenac Sodium, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system
(see
Chromatography 621)—The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 25-cm column containing packing L7 (end-capped). The flow rate is about 1 mL per minute. Chromatograph the
Resolution solution, and record the peak responses as directed for
Procedure: the relative retention times are about 0.5 for diethyl phthalate, 0.6 for diclofenac related compound A, and 1.0 for diclofenac; and the resolution,
R, between diethyl phthalate and diclofenac related compound A is not less than 2.2, and that between diclofenac related compound A and diclofenac is not less than 6.5. Chromatograph the
Standard solution, and record the peak responses as directed for
Procedure: the relative standard deviation for replicate injections is not more than 5%.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the peak responses over a period of 2.5 times the retention time of diclofenac. Calculate the percentage of diclofenac related compound A in the portion of Diclofenac Sodium taken by the formula:
10(C / W)(rU / rS),
in which
C is the concentration, in µg per mL, of
USP Diclofenac Related Compound A RS in the
Standard solution; W is the quantity, in mg, of Diclofenac Sodium taken to prepare the
Test solution; and
rU and
rS are the diclofenac related compound A peak responses obtained from the
Test solution and the
Standard solution, respectively: not more than 0.2% is found. Calculate the percentage of each other impurity in the portion of Diclofenac Sodium taken by the formula:
10(C / W)(ri / rS),
in which
ri is the response of an individual impurity peak obtained from the
Test solution, and the other terms are as defined above: not more than 0.2% of any individual impurity is found. The sum of all of the impurities found is not more than 0.5%.
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