Clofibrate
Propanoic acid, 2-(4-chlorophenoxy)-2-methyl-, ethyl ester. Ethyl 2-(p-chlorophenoxy)-2-methylpropionate ![]() ![]() ![]() » Clofibrate contains not less than 97.0 percent and not more than 103.0 percent of C12H15ClO3, calculated on the anhydrous basis.
Packaging and storage
Preserve in tight, light-resistant containers.
Identification
Solution:
20 µg per mL.
Medium:
methanol.
Refractive index
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Acidity
Mix 10.0 g with 100 mL of neutralized alcohol, add 3 drops of phenolphthalein TS, and titrate with 0.10 N sodium hydroxide: not more than 0.90 mL is required for neutralization.
Water, Method I
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Chromatographic purity
Standard preparation
Prepare a solution in chloroform having known concentrations of about 0.1 mg of USP Clofibrate RS and 0.03 mg of p-chlorophenol per mL. To 10.0 mL of this solution add 5.0 µL of tributyrin, and mix.
Test preparation
To 10.0 mL of Clofibrate add 5.0 µL of tributyrin, and mix.
Chromatographic system
(see Chromatography
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Procedure
[noteUse peak areas where peak responses are indicated.] Separately inject equal volumes (about 1 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity, other than p-chlorophenol, in the Clofibrate taken by the formula:
0.1C(RU / RS)
in which C is the concentration, in mg per mL, of USP Clofibrate RS in the Standard preparation, RU is the ratio of the response of each individual impurity peak (other than the p-chlorophenol peak) to that of the tributyrin peak obtained from the Test preparation, and RS is the ratio of the response of the clofibrate peak to that of the tributyrin peak obtained from the Standard preparation: the percentage of any impurity, other than p-chlorophenol, does not exceed 0.01%, and the total percentage of all such impurities does not exceed 0.12%.
Limit of p-chlorophenol
Use the chromatograms obtained in the test for Chromatographic purity. Calculate the percentage of p-chlorophenol in the portion of Clofibrate taken by the formula:
0.1C(RU / RS)
in which C is the concentration, in mg per mL, of p-chlorophenol in the Standard preparation, and RU and RS are the ratios of the responses of the p-chlorophenol and tributyrin peaks obtained from the Test preparation and the Standard preparation, respectively: not more than 0.003% of p-chlorophenol is found.
Assay
Ion-exchange resin
To a beaker containing 75 mL of 1 N sodium hydroxide add about 3 g of a 50- to 100-mesh strongly basic styrene-divinylbenzene anion-exchange resin, and allow the mixture to stand for about 15 minutes, with occasional stirring. Wash the resin with water until the last washing is neutral to litmus paper, then wash with three 50-mL portions of methanol.
Ion-exchange column
Place a plug of glass wool in the base of a 1- × 15-cm ion-exchange tube, and transfer to the tube a sufficient amount of Ion-exchange resin, slurried in methanol, to produce a column bed height of from 6 cm to 8 cm.
Standard preparation
Dissolve an accurately weighed quantity of USP Clofibrate RS in methanol, and dilute quantitatively and stepwise with methanol to obtain a solution having a known concentration of about 20 µg per mL.
Assay preparation
Transfer about 200 mg of Clofibrate, accurately weighed, to a 100-mL volumetric flask, add methanol to volume, and mix. Transfer 10.0 mL of this solution to the Ion-exchange column, and collect the eluate in a 100-mL volumetric flask. Rinse the column with 25 mL of methanol, collect the rinsing in the volumetric flask, dilute with methanol to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with methanol to volume, and mix.
Procedure
Concomitantly determine the absorbances of the Standard preparation and the Assay preparation in 1-cm cells at the wavelength of maximum absorbance at about 226 nm, with a suitable spectrophotometer, using methanol as the blank. Calculate the quantity, in mg, of C12H15ClO3 in the portion of Clofibrate taken by the formula:
10C(AU / AS)
in which C is the concentration, in µg per mL, of USP Clofibrate RS in the Standard preparation; and AU and AS are the absorbances of the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
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Chromatographic Column
USP32NF27 Page 1981
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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