Color of solution 
631
—
Reference solution—
Mix 5 mL of Matching Fluid G and 95 mL of dilute hydrochloric acid (1 in 40).
Test solution—
Transfer 500 mg of Fenofibrate to a 10-mL volumetric flask, dissolve in and dilute with acetone to volume, and mix.
Procedure—
Proceed as directed under
Color and Achromicity 631: the
Test solution is not more intensely colored than the
Reference solution.
Acidity—
Dissolve 1.0 g in 50 mL of alcohol previously neutralized to
phenolphthalein TS, and titrate with 0.1 N sodium hydroxide VS: not more than 0.2 mL of 0.1 N sodium hydroxide VS is required to change the color of the indicator to pink.
Chloride 221—
Test solution—
Add 25 mL of water to 5.0 g of Fenofibrate, and heat at 50
for 10 minutes. Cool, dilute with water to 50.0 mL, filter, and use the filtrate.
[note—Retain the remaining portion of the
Test solution for the test for
Sulfate.
]
Procedure—
Use 10 mL of the Test solution: it shows no more chloride than corresponds to 0.15 mL of 0.020 N hydrochloric acid (0.01%).
Related compounds—
Mobile phase—
Proceed as directed in the Assay.
Test solution—
Prepare as directed for the Assay preparation.
Chromatographic system (see Chromatography 621)—
Proceed as directed in the
Assay. In addition, chromatograph the
Impurity standard solution, and record the peak responses as directed for
Procedure: the resolution,
R, between fenofibrate related compound A and fenofibrate related compound B is not less than 1.5.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Impurity standard solution and the
Test solution into the chromatograph, record the chromatograms, and identify the fenofibrate peak and the peaks due to the impurities and degradation products listed in
Table 1.
Table 1
| Name |
Relative Retention Time |
Limit (%) |
| (4-Chlorophenyl)(4-hydroxyphenyl)methanone1 |
0.34 |
0.1 |
| 2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid (fenofibric acid)2 |
0.36 |
0.1 |
| (3RS)-3-[4-(4-Chlorobenzoyl)phenoxy]butan-2-one |
0.50 |
0.1 |
| Methyl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoate |
0.65 |
0.1 |
| Ethyl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-propanoate |
0.80 |
0.1 |
| (4-Chlorophenyl)[4-(1-methylethoxy)phenyl]methanone |
0.85 |
0.1 |
| 1-Methylethyl 2-[[2-[4-(4-chlorobenzoyl)phenoxy]-2-methylpropanoyl]oxy]-2-methylpropanoate3 |
1.35 |
0.2 |
| Any other impurity |
— |
0.1 |
|
1
Fenofibrate related compound A
|
|
2
Fenofibrate related compound B
|
|
3
Fenofibrate related compound C
|
Measure the responses for the major peaks, and calculate the percentage of each of fenofibrate related compound A, fenofibrate related compound B, and fenofibrate related compound C in the portion of Fenofibrate taken by the formula:
10C/W(rU / rS)
in which
C is the concentration, in µg per mL, of the appropriate fenofibrate related compound in the
Impurity standard solution; W is the weight, in mg, of fenofibrate taken to prepare the
Test solution; and
rU and
rS are the peak responses of the appropriate fenofibrate related compound obtained from the
Test solution and the
Impurity standard solution, respectively.
Calculate the percentage of any other impurity in the portion of Fenofibrate taken by the formula:
10C/W(rU / rS)
in which
C is the concentration, in µg per mL, of fenofibrate in the
Impurity standard solution; W is as defined above;
rU is the peak response for each impurity obtained from the
Test solution; and
rS is the peak response of fenofibrate obtained from the
Impurity standard solution. In addition to not exceeding the limits for each impurity in
Table 1, not more than 0.5% of total impurities is found.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile and water acidified with phosphoric acid to a pH of 2.5 (70: 30). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Fenofibrate RS in
Mobile phase, and dilute quantitatively, and stepwise if necessary, with
Mobile phase to obtain a solution having a known concentration of about 1.0 mg per mL.
Assay preparation—
Transfer about 100 mg of Fenofibrate, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 286-nm detector and a 4.0-mm × 25-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the relative standard deviation for six replicate injections is not more than 1.0%.
Procedure—
Separately inject equal volumes (about 5 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C
20H
21ClO
4 in the portion of Fenofibrate taken by the formula:
100C(rU / rS)
in which
C is the concentration, in mg per mL, of
USP Fenofibrate RS in the
Standard preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
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