Medium-Chain Triglycerides

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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1 DEFINITION

Medium-Chain Triglycerides consist of a mixture of triglycerides of saturated fatty acids, mainly of caprylic acid (C₈H₁₆O₂) and capric acid (C₁₀H₂₀O₂). The fatty acids are derived from the oil extracted from the hard, dried fraction of the endosperm of Cocos nucifera L. or from the dried endosperm of Elaeis guineensis Jacq. They contain NLT 95% of saturated fatty acids with 8 and 10 carbon atoms.

2 IDENTIFICATION

A. (NF 1-May-2020) Meet the requirements in Specific Tests for Fats and Fixed Oils 〈401〉, Procedures, Fatty Acid Composition

3 IMPURITIES

Limit of Chromium, Copper, Lead, and Nickel

[Note—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]

Internal standard solution:

Transfer 2.0 mL of a solution containing 1000 mg/L of yttrium and 2.0 mL of a solution containing 1000 mg/L of lutetium to a 1000-mL volumetric flask, add 10 mL of 65% ultratrace nitric acid, dilute with water to volume, and mix.

Blank standard:

Transfer 1.0 mL of the Internal standard solution to a 100-mL volumetric flask, add 10.0 mL of 65% ultratrace nitric acid, dilute with water to volume, and mix.

Standard stock solution:

Transfer 1.0 mL each of the solutions containing 1000 mg/L of chromium, copper, lead, and nickel to a 100-mL volumetric flask, add 10.0 mL of 65% ultratrace nitric acid, dilute with water to volume, and mix. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, add 10 mL of 65% ultratrace nitric acid, dilute with water to volume, and mix. The concentration of each element in this solution is 100 µg/L.

Standard solutions:

Into two separate 100-mL volumetric flasks, transfer 1.0 mL and 5.0 mL of the Standard stock solution, add 1.0 mL of the Internal standard solution and 10.0 mL of 65% ultratrace nitric acid, dilute with water to volume, and mix well. The concentration of each element in these solutions is 1 µg/L and 5 µg/L, respectively.

Sample solution:

Transfer 3.5 g of Medium-Chain Triglycerides into a suitable quartz flask. Add 5 mL of concentrated sulfuric acid and heat slowly on a hot-plate in a fume hood. At the boiling heat, carefully add 5 mL of 30% Hydrogen peroxide in 1-mL increments. Continue heating until the solution is clear and colorless. Otherwise, add another 3 mL of concentrated sulfuric acid and continue to add more 30% hydrogen peroxide. After cooling, cautiously add about 5 mL of water dropwise. Quantitatively transfer the flask’s contents into a clean, dry, 20-mL volumetric flask, dilute with water to volume, and mix. Transfer 1.0 mL of digestion solution to a 20-mL volumetric flask, add 0.2 mL of the Internal standard solution and 2.0 mL of 65% ultratrace nitric acid, dilute with water to volume, and mix. Retain the remaining digestion solution for use in the test for Limit of Tin.

Blank solution:

Prepare the blank digestion solution, following the preparation procedure for the Sample solution, but without using Medium-Chain Triglycerides.

Instrumental conditions

(See Plasma Spectrochemistry 〈730〉.)

Mode: ICP–MS

Spectrometer: Quadrupole mass spectrometer

Detector: Ion detector maintained under vacuum

System suitability

Samples: Blank standard and Standard solutions

Suitability requirements: Instrument performance must be verified to conform to the manufacturer’s specifications for resolution and sensitivity. Before analyzing the Sample solutions, the instrument must pass a suitable performance check. The instrument should read all isotopes for the following elements shown in Table 1 for the yttrium internal standard (89 amu) and the lutetium internal standard (175 amu), and should report the total element contents using the isotopes. Generate the calibration curve using the Blank standard and Standard solutions for each element. The linear regression coefficient is NLT 0.99.

Analysis

Samples: Blank solution and Sample solution

Determine the concentration of each element in the Blank solution and in the Sample solution using the calibration curve.

Calculate the quantity, in µg/g, of each element in the portion of Medium-Chain Triglycerides taken:

Result = (Cₛ − C_ᴮ)/Cₘ

Cₛ = concentration of each element in the Sample solution (µg/L)

C_ᴮ= concentration of each element in the Blank solution (µg/L)

Cₘ = concentration of Medium-Chain Triglycerides in the Sample solution (g/L)

Acceptance criteria:

See Table 2.

Limit of Tin

[Note—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]

Proceed as directed in the test for Limit of Chromium, Copper, Lead, and Nickel.

Blank standard:

Transfer 1.0 mL of the Internal standard solution to a 100-mL volumetric flask, add 10.0 mL of 30% hydrochloric acid, dilute with water to volume, and mix.

Standard stock solution:

Transfer 1.0 mL of a solution containing 1000 mg/L of tin to a 100-mL volumetric flask, add 25.0 mL of 30% hydrochloric acid, dilute with water to volume, and mix. Transfer 1.0 mL of this solution to a 100-mL volumetric flask, add 25.0 mL of 30% hydrochloric acid, dilute with water to volume, and mix. The concentration of tin in this solution is 100 µg/L.

Standard solutions:

Into two separate 100-mL volumetric flasks, transfer 1.0 mL and 5.0 mL of the Standard stock solution, add 1.0 mL of the Internal standard solution and 25.0 mL of 30% hydrochloric acid, dilute with water to volume, and mix well. The concentration of tin in these solutions is 1 µg/L and 5 µg/L, respectively.

Acceptance criteria:

NMT 0.1 µg/g

Alkaline Impurities

Sample solution:

Dissolve 2.0 g of Medium-Chain Triglycerides in a mixture of alcohol and ethyl ether (1.5:3.0).

Analysis:

Add 0.05 mL of bromophenol blue TS to the Sample solution, and titrate with 0.01 N hydrochloric acid VS (NF 1-May-2020) to a yellow endpoint.

Acceptance criteria:

NMT 0.15 mL of 0.01 N hydrochloric acid VS (NF 1-May-2020) is required.

4 SPECIFIC TESTS

Fats and Fixed Oils 〈401〉, Procedures, Unsaponifiable Matter

Sample: 5.0 g

Acceptance criteria: NMT 0.5% (NF 1-May-2020)

Specific Gravity 〈841〉: 0.93–0.96 at 20°C

Water Determination 〈921〉, Method I: NMT 0.2%

Appearance

Diluent: Hydrochloric acid and water (2.75%:97.25%)

Sample: 10 mL

Standard solution: Prepare immediately before use by mixing 2.4 mL of ferric chloride CS and 0.6 mL of cobaltous chloride CS with Diluent to make 10.0 mL, and diluting 5.0 mL of the solution with Diluent to make 10.0 mL.

Analysis: Compare the Sample and the Standard solution by viewing them downward in matched color–comparison tubes against a white surface (see Color and Achromicity 〈631〉).

Acceptance criteria: The Sample is clear and not more intensely colored than the Standard solution.

Fats and Fixed Oils 〈401〉, Procedures, Acid Value: NMT 0.2

Fats and Fixed Oils 〈401〉, Procedures, Fatty Acid Composition:

The fatty acid fraction of Medium-Chain Triglycerides exhibits the following composition as seen in Table 3. Disregard any peak with an area less than 0.05% of the total area.

Fats and Fixed Oils 〈401〉, Procedures, Hydroxyl Value: NMT 10

Fats and Fixed Oils 〈401〉, Procedures, Iodine Value: NMT 1.0

Fats and Fixed Oils 〈401〉, Procedures, Peroxide Value: NMT 1.0

Fats and Fixed Oils 〈401〉, Procedures, Saponification Value

Sample: 1.0 g

Acceptance criteria: 310–360 (NF 1-May-2020)

Viscosity—Capillary Methods 〈911〉

Analysis: Determine at 20 ± 0.1°C with a capillary viscometer.

Acceptance criteria: 25–33 mPa·s

Articles of Botanical Origin 〈561〉, Methods of Analysis, Total Ash

Sample: 2.0 g

Acceptance criteria: NMT 0.1%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at temperatures not exceeding 25°C.

Labeling: Where Medium-Chain Triglycerides is intended for use in the manufacture of injectable dosage forms or parenteral nutrition therapy, it is so labeled. (NF 1-May-2020)

Reference standards and additional notes (as in original):

Suitable yttrium ICP standard is available from LGC or Millipore Sigma.

Suitable lutetium ICP standard is available from LGC or Millipore Sigma.

Suitable single-element ICP standards are available from LGC or Millipore Sigma.

Suitable ultratrace concentrated sulfuric acid is available from Spectrum Chemicals or Millipore Sigma.

Suitable ultratrace 30% hydrogen peroxide is available from Spectrum Chemicals or Millipore Sigma.

Suitable ultratrace 30% hydrochloric acid is available from Spectrum Chemicals, Millipore Sigma, WVR, or other vendors.

Suitable tin ICP standard is available from LGC or Millipore Sigma.