Fenofibrate Capsules
DEFINITION
Fenofibrate Capsules contains NLT 90.0% and NMT 110.0% of the labeled amount of fenofibrate (C20H21ClO4).
IDENTIFICATION
•  The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
•  Procedure
[Note—Use Sample stock solution 2 for Capsules labeled to meet the requirements of Dissolution Test 2. For all other products, use Sample stock solution 1. ]
Solution A:  136 mg/L of monobasic potassium phosphate in water. Adjust with dilute phosphoric acid (1 in 10) to a pH of 2.9 ± 0.05.
Mobile phase:  Methanol and Solution A (4:1)
Standard solution:  67 µg/mL of USP Fenofibrate RS in Mobile phase
Sample stock solution 1:  Accurately weigh the contents of NLT 20 Capsules. Mix the contents, and transfer a weighed portion of the powder, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask. Add 80 mL of Mobile phase, sonicate for 10 min, stir for 15 min, and dilute with Mobile phase to volume.
Sample stock solution 2 (For Capsules labeled to meet the requirements of Dissolution Test 2) Weigh the contents of NLT 20 Capsules. Mix the contents, melt in an oven at 80 for NLT 30 min, and homogenize. Allow the sample to solidify. Transfer a weighed portion of the sample, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask, dissolve in 30 mL of methanol with the aid of a mechanical shaker for NLT 4 h, and dilute with Mobile phase to volume.
Sample solution:  67 µg/mL of fenofibrate from the designated Sample stock solution, in Mobile phase. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, discarding the first 5 mL.
Chromatographic system 
Mode:  LC
Detector:  UV 285 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Flow rate:  1 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Column efficiency:  NLT 6000 theoretical plates
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C20H21ClO4 in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of the Standard solution (µg/mL)
CU== nominal concentration of the Sample solution (µg/mL)
Acceptance criteria:  90.0%–110.0%
PERFORMANCE TESTS
•  Dissolution 711
Test 1 
Medium:  0.05 M sodium lauryl sulfate in water; 1000 mL, deaerated
Apparatus 2:  75 rpm
Time:  40 min
Solution A and Mobile phase:  Proceed as directed in the Assay.
Standard solution:  (0.001 × L) mg/mL of USP Fenofibrate RS in Mobile phase, where L is the Capsule label claim, in mg
Sample solution:  Pass a portion of the solution under test through a suitable polyvinylidene difluoride (PVDF) filter of 0.45-µm pore size.
Chromatographic system 
Mode:  LC
Detector:  UV 285 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Flow rate:  1 mL/min
Injection size:  10 µL for Capsules labeled to contain 67 mg; 5 µL for Capsules labeled to contain 134 or 200 mg
System suitability 
Sample:  Standard solution
Suitability requirements 
Column efficiency:  NLT 4000 theoretical plates
Tailing factor:  NMT 2.0
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C20H21ClO4 dissolved:
Result = (rU/rS) × CS × V × (100/L)
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of the Standard solution (mg/mL)
V== volume of Medium, 1000 mL
L== Capsule label claim (mg)
Tolerances:  NLT 70% (Q) of the labeled amount of C20H21ClO4 is dissolved.
Test 2:   If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:  Phosphate buffer pH 6.8 ± 0.1 containing 0.1% pancreatin and 2% polysorbate 80; 900 mL, deaerated by vacuum
Apparatus 2:  75 rpm with sinkers (see Dissolution 711, Figure 2a)
Time:  2 h
Detector:   UV 288 nm
Standard solution:  (L/1000) mg/mL of USP Fenofibrate RS in Medium, where L is the Capsule label claim, in mg. A volume of methanol, not exceeding 10%, can be used in the first dilution to solubilize fenofibrate.
Sample solution:  Pass 20 mL of the solution under test through a suitable PVDF filter of 0.45-µm pore size, discarding the first 2 mL.
Path length:  0.1 cm, flow cell
Blank:  Medium
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of C20H21ClO4 dissolved:
Result = (AU/AS) × CS × V × (100/L)
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
V== volume of Medium, 900 mL
L== Capsule label claim (mg)
Tolerances:  NLT 80% (Q) of the labeled amount of C20H21ClO4 is dissolved.
Test 3:  If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 3.
Medium:  0.72% sodium lauryl sulfate in water; 1000 mL, deaerated
Apparatus 2:  75 rpm, with sinkers with three prongs
Time:  30 min
Standard solution:  L/10 mg/mL of USP Fenofibrate RS in methanol, where L is the Capsule label claim in mg. Transfer 10.0 mL of this solution to a 1000-mL volumetric flask, and dilute with Medium to volume.
Sample solution:  Pass a portion of the solution under test through a suitable PVDF filter of 0.45-µm pore size. Dilute with Medium, if necessary.
Detection:  UV 290 nm
Blank:  Medium
Calculate the percentage of fenofibrate dissolved:
Result = (AU/AS) × (CS/L) × D × V × 100
AU== absorbance of the Sample solution
AS== absorbance of the Standard solution
CS== concentration of the Standard solution (mg/mL)
L== Capsule label claim (mg)
D== dilution for the Sample solution
V== volume of the Medium, 1000 mL
Tolerances:  NLT 80% (Q) of the labeled amount of fenofibrate is dissolved.
•  Uniformity of Dosage Units 905: Meet the requirements
Procedure for content uniformity 
Solution A, Mobile phase, Standard solution, Chromatographic system, System suitability, and Analysis:  Proceed as directed in the Assay, except to prepare the Sample stock solution and Sample solution as follows.
Sample stock solution:  Place 1 Capsule in a suitable volumetric flask, add Solution A to 10%–20% of the final volume, and stir for 20 min to disintegrate the Capsule. Fill the flask to about 80% with methanol, sonicate for 10 min, stir for 15 min, and dilute with methanol to volume to obtain a solution having a known concentration of about 0.4–0.7 mg/mL of fenofibrate, based on the label claim.
Sample solution:  60–70 µg/mL of fenofibrate, from the Sample stock solution, in Mobile phase. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, discarding the first 5 mL.
IMPURITIES
Organic Impurities  
[Note—Use Sample solution 2 for Capsules labeled to meet the requirements of Dissolution Test 2. For all other products, use Sample solution 1. ]
•  Procedure
Solution A:  136 mg/L of monobasic potassium phosphate. Adjust with dilute phosphoric acid (1 in 10) to a pH of 2.9 ± 0.05.
Mobile phase:  Methanol and Solution A (4:1)
Standard solution:  3.35 µg/mL of USP Fenofibrate RS and 3.35 µg/mL of USP Fenofibrate Related Compound B RS in Mobile phase
System suitability solution:  0.67 mg/mL of USP Fenofibrate RS and 3.35 µg/mL of USP Fenofibrate Related Compound B RS in Mobile phase
Quantitative limit solution:  0.67 µg/mL of USP Fenofibrate RS and 0.67 µg/mL of USP Fenofibrate Related Compound B RS in Mobile phase, from the Standard solution
Sample solution 1:  Accurately weigh the contents of NLT 20 Capsules. Mix the contents, and transfer a weighed portion of the powder, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask. Add 80 mL of Mobile phase, sonicate for 10 min, stir for 15 min, and dilute with Mobile phase to volume. Pass a portion of this solution through a PVDF filter of 0.45-µm pore size, discarding the first 5 mL. The final concentration based on the label claim is about 0.67 mg/mL.
Sample solution 2 (For Capsules labeled to meet the requirements of Dissolution Test 2) Weigh the contents of NLT 20 Capsules. Mix the contents, melt in an oven at 80 for NLT 30 min, and homogenize. Allow the sample to solidify. Transfer a weighed portion of the sample, equivalent to about 67 mg of fenofibrate, to a 100-mL volumetric flask, dissolve in 30 mL of methanol with the aid of a mechanical shaker for NLT 4 h, and dilute with Mobile phase to volume. Pass through a PVDF filter of 0.45-µm pore size, discarding the first 1–2 mL. The final concentration based on the label claim is about 0.67 mg/mL.
Chromatographic system 
Mode:  LC
Detector:  UV 285 nm
Column:  4.6-mm × 15-cm; 5-µm packing L1
Flow rate:  1 mL/min
Injection size:  20 µL
System suitability 
Samples:  Standard solution, System suitability solution, and Quantitative limit solution
Suitability requirements 
Resolution:  NLT 3.0 between fenofibrate and fenofibrate related compound B, System suitability solution
Column efficiency:  NLT 3000 theoretical plates for fenofibrate related compound B, System suitability solution
Tailing factor:  NMT 2.0 for fenofibrate related compound B, System suitability solution
Relative standard deviation:  NMT 2.0%, Standard solution
Signal-to-noise ratio:  NLT 10 for the fenofibrate peak, Quantitative limit solution
Analysis 
Samples:  Standard solution and designated Sample solution
Calculate the percentage of fenofibrate related compound B in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of fenofibrate related compound B from the Sample solution
rS== peak response of fenofibrate related compound B from the Standard solution
CS== concentration of fenofibrate related compound B in the Standard solution (mg/mL)
CU== nominal concentration of fenofibrate in the Sample solution (mg/mL)
Calculate the percentage of any other impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of each individual impurity from the Sample solution
rS== peak response of fenofibrate from the Standard solution
CS== concentration of fenofibrate in the Standard solution (mg/mL)
CU== nominal concentration of fenofibrate in the Sample solution (mg/mL)
Acceptance criteria 
Individual impurities:  NMT 0.5% for fenofibrate related compound B; NMT 0.2% for any other individual impurity
Total impurities:  NMT 2.0%
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed containers, and store at controlled room temperature.
•  Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.
•  USP Reference Standards 11
USP Fenofibrate RS Click to View Structure
USP Fenofibrate Related Compound B RS Click to View Structure
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid, or fenofibric acid.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Elena Gonikberg, Ph.D.
Principal Scientific Liaison
1-301-816-8251
(SM32010) Monographs - Small Molecules 3
711 Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison
1-301-816-8106
(GCDF2010) General Chapters - Dosage Forms
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 3161
Pharmacopeial Forum: Volume No. 34(2) Page 258