Add the following:Fish Oil Containing Omega-3 Acids Delayed-Release Capsules
Fish Oil Containing Omega-3 Acids Delayed-Release Capsules are enteric-coated Capsules that contain NLT 95.0% and NMT 105.0% of the labeled amount of Fish Oil Containing Omega-3 Acids where Fish Oil Containing Omega-3 Acids is the purified, winterized, and deodorized fatty oil obtained from fish of the families Engraulidae, Carangidae, Clupeidae, Osmeridae, Scombroidae, and Ammodytidae. The omega-3 acids are defined as the following: alpha-linolenic acid (C18:3 n3), moroctic acid (C18:4 n3), eicosatetraenoic acid (C20:4 n3), eicosapentaenoic acid (EPA) (C20:5 n3), heneicosapentaenoic acid (C21:5 n3), docosapentaenoic acid (C22:5 n3), and docosahexaenoic acid (DHA) (C22:6 n3). It contains NLT 28.0% (w/w) of total omega-3 acids, expressed as free acids, consisting of NLT 13.0% of EPA and NLT 9.0% of DHA. Suitable antioxidants in appropriate concentrations may be added.
• A. The oil contained in the Capsules meets the requirements for the following test: The retention times of the peaks for eicosapentaenoic acid methyl ester and docosahexaenoic acid methyl ester obtained in the chromatogram of Test Solution 2 in the test for Content of EPA and DHA correspond to those for the respective compounds in the chromatogram of Standard Solution 1. The sum of the area for EPA and DHA methyl esters is NLT 22% of the total detected area for the methyl esters, and no other peak has an area higher than 20% of the total detected area for the methyl esters. The chromatogram of Test Solution 2 exhibits at least 15 additional peaks at the retention times of the methyl esters of unsaturated fatty acids exhibited in Standard Solution 2.
• Content of Fish Oil: Weigh NLT 10 Capsules in a tared weighing bottle, carefully open the Capsules, without loss of shell material, and transfer the combined Capsule contents to a 100-mL beaker. Remove any adhering substance from the emptied Capsules by washing with several small portions of 2,2,4-trimethylpentane. Discard the washings, and allow the empty Capsules to dry in a current of dry air until the 2,2,4-trimethylpentane is completely evaporated. Weigh the empty Capsules in the original tared weighing bottle, and calculate the average net weight per Capsule.
Acceptance criteria: 95.0%105.0% of the labeled amount
• Content of EPA and DHA
Samples: Standard Solution 1, Standard Solution 2, Test Solution 1, and Test Solution 2
Identify the retention times of the relevant fatty acid methyl esters peaks by comparing the chromatogram of Standard Solution 2 with the reference chromatogram supplied with the USP Fish Oil RS. Identify the retention time for the internal standard peak from Test Solution 2 by comparing with that of Test Solution 1.
Calculate the percentage of EPA or DHA in the portion of fish oil containing omega-3 acids taken from the Capsules:
Result = (RU/RS) × (WS/WU) × F × 100
RU = 1/[(rU2/rT2) (rU1/rT1)]
Acceptance criteria: NLT 13.0% (w/w) of EPA and NLT 9.0% (w/w) of DHA
• Content of Total Omega-3 Acids
Analysis: Proceed as directed in the test for Content of EPA and DHA.
Calculate the percentage of the total omega-3 acids in the portion of fish oil containing omega-3 acids taken from the Capsules:
Result = EPA + DHA + [An3(EPA + DHA)]/(AEPA + ADHA)
Acceptance criteria: NLT 28.0% (w/w) of total omega-3 acids, expressed as free acids
• Weight Variation 2091: Meet the requirements
• Disintegration and Dissolution 2040: Meet the requirements for Disintegration, Delayed-Release (Enteric-Coated) Soft Shell Capsules
• Fats and Fixed Oils, Trace Metals 401: NMT 0.1 ppm each of Pb, Cd, As, and Hg
• Limit of Dioxins, Furans, and Polychlorinated Biphenyls
Analysis: Determine the content of polychlorinated dibenzo-para-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) by method No. 1613 revision B of the Environmental Protection Agency. Determine the content of polychlorinated biphenyls (PCBs) by method No. 1668 revision A of the Environmental Protection Agency.
Acceptance criteria: The sum of PCDDs and PCDFs is NMT 2.0 pg/g of WHO toxic equivalents. The sum of PCDDs, PCDFs, and dioxin-like PCBs (polychlorinated biphenyls, non-ortho IUPAC congeners PCB-77, PCB-81, PCB-126, and PCB-169, and mono-ortho IUPAC congeners PCB-105, PCB-114, PCB-118, PCB-123, PCB-156, PCB-157, PCB-167, and PCB-189) is NMT 10.0 pg/g of WHO toxic equivalents.
• Fats and Fixed Oils, Acid Value 401: NMT 3
• Fats and Fixed Oils, Anisidine Value 401: NMT 20.0
• Fats and Fixed Oils, Peroxide Value 401: NMT 5.0
• Fats and Fixed Oils, Total Oxidation Value (TOTOX) 401: NMT 26, calculated:
Result = (2 × PV) + AV
• Fats and Fixed Oils, Unsaponifiable Matter 401: NMT 1.5%
• Stearin: 10 mL remains clear after cooling at 0 for 3 h.
Sample solution: 0.24 mg/mL in isooctane
Acceptance criteria: NMT 0.70, determined at 233 nm
• Packaging and Storage: Preserve in tight containers, and store at room temperature, protected from light.
• Labeling: The label states the amount of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in mg/Capsule.
• USP Reference Standards 11USP35
USP Docosahexaenoic Acid Ethyl Ester RS
all cis-4,7,10,13,16,19-Docosahexaenoic ethyl ester.
USP Eicosapentaenoic Acid Ethyl Ester RS
all cis-5,8,11,14,17-Eicosapentaenoic ethyl ester.
USP Fish Oil RS
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 1297Pharmacopeial Forum: Volume No. 36(6) Page 1594