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.

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%).

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. 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: 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.

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: 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.