» Fenofibrate contains not less than 98.5 percent and not more than 101.0 percent of C20H21ClO4, calculated on the dried basis.
Packaging and storage Preserve in well-closed, light-resistant containers. Store at room temperature.
USP Reference standards 11
USP Fenofibrate RS .
USP Fenofibrate Related Compound A RS .
USP Fenofibrate Related Compound B RS .
USP Fenofibrate Related Compound C RS .
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.
Identification, Infrared Absorption 197K.
Melting range, Class 1a 741: between 79 and 82.
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.
Loss on drying 731 Dry it in vacuum over phosphorus pentoxide at 60 to constant weight: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%, determined on 1.0 g.
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. [noteRetain 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%).
Sulfate 221 Use 10 mL of the Test solution retained from the test for Chloride: it shows no more sulfate than corresponds to 0.15 mL of 0.020 N sulfuric acid (0.01%).
Heavy metals, Method II 231: 0.002%.
Mobile phase Proceed as directed in the Assay.
Impurity standard solution Dissolve accurately weighed quantities of USP Fenofibrate RS, USP Fenofibrate Related Compound A RS, USP Fenofibrate Related Compound B RS, and USP Fenofibrate Related Compound C RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having known concentrations of about 1 µg per mL each of fenofibrate, fenofibrate related compound A, and fenofibrate related compound B, and about 2 µg per mL of fenofibrate related compound C.
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.
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.
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 C20H21ClO4 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.
Auxiliary Information Please check for your question in the FAQs before contacting USP.Chromatographic Column
USP32NF27 Page 2351Pharmacopeial Forum: Volume No. 31(3) Page 763
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.