Medium-Chain Triglycerides

Glycerides,mixed decanoyl and octanoyl.
Caprylic and capric triglycerides.
»Medium-Chain Triglycerides are obtained from the oil extracted from the hard,dried fraction of the endosperm of Cocos nucifera L.or from the dried endosperm of Elaeis guineensisJacq.They consist of a mixture of triglycerides of saturated fatty acids,mainly of caprylic acid (C8H16O2)and of capric acid (C10H20O2).They contain not less than 95percent of saturated fatty acids with 8and 10carbon atoms.
Packaging and storage— Preserve in tight containers,protected from light.Store at temperatures not exceeding 25.
Labeling— Where it is intended for use in parenteral nutrition,it is so labeled.
Appearance— The substance is clear and not more intensely colored than a solution prepared immediately before use by mixing 2.4mLof ferric chloride CSand 0.6mLof cobaltous chloride CSwith Diluentto make 10.0mL,and diluting 5.0mLof the solution so obtained with Diluentto make 10.0mL.Make the comparison by viewing the substance and the solution downward in matched color-comparison tubes against a white surface (see Color and Achromicity á631ñ).
Diluent— Transfer 27.5mLof hydrochloric acid to a 1000-mLvolumetric flask,and dilute with water to volume.
Identification—
A: It meets the requirements of the test for Saponification value.
B: It meets the requirements of the test for Fatty acid composition.
Specific gravity á841ñ: between 0.93and 0.96,at 20.
Acid value á401ñ: not more than 0.2.
Hydroxyl value á401ñ: not more than 10.
Iodine value á401ñ: not more than 1.0.
Peroxide value á401ñ: not more than 1.0.
Saponification value á401ñ: between 310and 360,determined on 1.0g.
Unsaponifiable matter á401ñ: not more than 0.5%,determined on 5.0g.
Fatty acid composition á401ñ The fatty acid fraction of Medium-Chain Triglycerides exhibits the following composition,as determined in the section Fatty Acid Composition.Disregard any peak with an area less than 0.05%of the total area:
Carbon-Chain Length Number of Double Bonds Percentage (%)
6 0 £2.0
8 0 50.0–80.0
10 0 20.0–50.0
12 0 £3.0
14 0 £1.0
Viscosity á911ñ: between 25and 33centipoises determined at 20±0.1with a capillary viscosimeter.
Refractive index á831ñ: between 1.440and 1.452,at 20.
Alkaline impurities— Dissolve 2.0g of Medium-Chain Triglycerides in a mixture of 1.5mLof alcohol and 3.0mLof ethyl ether.Add 0.05mLof bromophenol blue TS,and titrate with 0.01Nhydrochloric acid to a yellow endpoint:not more than 0.15mLof 0.01Nhydrochloric acid is required.
Water,Method Iá921ñ: not more than 0.2%.
Total ash á561ñ: not more than 0.1%,determined on 2.0g.
Heavy metals,Method IIá231ñ [NOTE—Use this test for Medium-Chain Triglycerides intended for use other than in parenteral nutrition.]
Test solution— Transfer 2.0g of Medium-Chain Triglycerides to a quartz crucible,add 0.5g of magnesium oxide,and mix.Ignite the crucible to dull redness until a homogeneous white or grayish-white mass is obtained.Ignite at 800for 1hour,cool,and dissolve the residue by adding two 5-mLportions of diluted hydrochloric acid.Add 0.1mLof phenolphthalein TSand then ammonium hydroxide until a pink color is obtained.Cool,add glacial acetic acid until the solution is decolorized,then add 0.5mLin excess,and dilute with water to 20.0mL.
Standard solution— To 0.5g of magnesium oxide add 2.0mLof Standard Lead Solution,and evaporate to dryness at 105for 1hour.Using the same conditions as prescribed for the Test solution,ignite,dissolve in diluted hydrochloric acid,add ammonia and then acetic acid,and dilute with water to 20.0mL.
Procedure— To 12mLof the Test solution,add 2.0mLof pH3.5Acetate Buffer,mix,add to 1.2mLof thioacetamide-glycerin base TS,and mix immediately.To 10mLof the Standard solution,add 2.0mLof the Test solution,add 2.0mLof pH3.5Acetate Buffer,mix,add to 1.2mLof thioacetamide-glycerin base TS,and mix immediately.Prepare a blank,using a mixture of 10mLof water and 2.0mLof the Test solution.Compared to the blank,the Standard solutionshows a light brown color.Dilute both the Test solutionand the Standard solutionwith water to 50mL,allow to stand for 2minutes,and view downward over a white surface:any brown color from the Test solutionis not darker than that of the solution from the Standard solution(not more than 10µg per g).
Limit of chromium— [NOTE—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]
Test stock solution— Transfer about 50g of Medium-Chain Triglycerides to a 100-mLvolumetric flask,dissolve in and dilute with diisobutyl ketone to volume.
Test solution— Transfer 4.0mLof Test stock solutionto a 10-mLvolumetric flask,and dilute with diisobutyl ketone to volume.
Chromium standard solution— Transfer about 0.283g of potassium dichromate,previously dried at 105for 4hours and accurately weighed,to a 1000-mLvolumetric flask,and dilute with water to volume.Immediately before use,dilute this solution with water to 1000times its volume.This solution contains the equivalent of 0.1µg of chromium per mL.
Standard solutions— Into each of three 10-mLvolumetric flasks,transfer 4.0mLof Test stock solution,add 0.5,1.0,and 2.0mL,respectively,of Chromium standard solution,and dilute with diisobutyl ketone to volume.These solutions contain 0.005µg,0.01µg,and 0.02µg of chromium per mL,respectively.
Procedure— Concomitantly determine the absorbances of the Standard solutionsand the Test solutionat least three times each,at the wavelength of maximum absorbance at 357.8nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a graphite furnace and a chromium hollow-cathode lamp,using argon as the carrier gas.Record the average of the steady readings for each of the Standard solutionsand the Test solution.Plot the absorbances of the Standard solutionsand the Test solutionversus the concentration of added chromium.Draw the straight line best fitting the points,and extrapolate the line until it meets the concentration axis.The distance between this point and the intersection of the axes represents the concentration of chromium in the Test solution.Not more than 0.05µg per g is found.
Limit of copper— [NOTE—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]
Test stock solution andTest solution— Proceed as directed in the test for Limit of chromium.
Copper standard solution— Transfer about 0.393g of cupric sulfate,accurately weighed,to a 1000-mLvolumetric flask,and dilute with water to volume.Immediately before use,dilute this solution with water to 1000times its volume.This solution contains the equivalent of 0.1µg of copper per mL.
Standard solutions— Into each of three 10-mLvolumetric flasks,transfer 4.0mLof Test stock solution,add 1.0,2.0,and 4.0mL,respectively,of Copper standard solution,and dilute with diisobutyl ketone to volume.These solutions contain 0.01µg,0.02µg,and 0.04µg of copper per mL,respectively.
Procedure— Concomitantly determine the absorbances of the Standard solutionsand the Test solutionat least three times each,at the wavelength of maximum absorbance at 324.7nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a graphite furnace and a copper hollow-cathode lamp,using argon as the carrier gas.Record the average of the steady readings for each of the Standard solutionsand the Test solution.Plot the absorbances of the Standard solutionsand the Test solutionversus the concentration of added copper.Draw the straight line best fitting the points,and extrapolate the line until it meets the concentration axis.The distance between this point and the intersection of the axes represents the concentration of copper in the Test solution.Not more than 0.1µg per g is found.
Limit of lead— [NOTE—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]
Test stock solution andTest solution— Proceed as directed in the test for Limit of chromium.
Lead standard solution— Dissolve 160mg of lead nitrate in 100mLof water that contains 1mLof lead-free nitric acid,and dilute with water to 1000mL.Pipet 10mLof this solution into a 100-mLvolumetric flask,dilute with water to volume,and mix.Immediately before use,dilute this solution with water to 100times its volume.This solution contains the equivalent of 0.1µg of lead per mL.
Standard solutions— Into each of three 10-mLvolumetric flasks,transfer 4.0mLof Test stock solution,add 1.0,2.0,and 4.0mL,respectively,of Lead standard solution,and dilute with diisobutyl ketone to volume.These solutions contain 0.01µg,0.02µg,and 0.04µg of lead per mL,respectively.
Procedure— Concomitantly determine the absorbances of the Standard solutionsand the Test solutionat least three times each,at the wavelength of maximum absorbance at 283.3nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a graphite furnace coated inside with palladium carbide and a lead hollow-cathode lamp,using argon as the carrier gas.Calcination is carried out in the presence of oxygen at a temperature below 800.Record the average of the steady readings for each of the Standard solutionsand the Test solution.Plot the absorbances of the Standard solutionsand the Test solutionversus the concentration of added lead.Draw the straight line best fitting the points,and extrapolate the line until it meets the concentration axis.The distance between this point and the intersection of the axes represents the concentration of lead in the Test solution.Not more than 0.1µg per g is found.
Limit of nickel— [NOTE—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]
Test stock solution andTest solution— Proceed as directed in the test for Limit of chromium.
Nickel standard solution— Immediately before use,dilute 10mLof nickel standard solution TSwith water to 1000mL.This solution contains the equivalent of 0.1µg of nickel per g.
Standard solutions— Into each of three 10-mLvolumetric flasks,transfer 4.0mLofTest stock solution,add 1.0,2.0,and 4.0mL,respectively,of Nickel standard solution,and dilute with diisobutyl ketone to volume.These solutions contain 0.01µg,0.02µg,and 0.04µg of nickel per mL,respectively.
Procedure— Concomitantly determine the absorbances of the Standard solutionsand the Test solutionat least three times each,at the wavelength of maximum absorbance at 232nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a graphite furnace and a nickel hollow-cathode lamp,using argon as the carrier gas.Record the average of the steady readings for each of the Standard solutionsand the Test solution.Plot the absorbances of the Standard solutionsand the Test solutionversus the concentration of added nickel.Draw the straight line best fitting the points,and extrapolate the line until it meets the concentration axis.The distance between this point and the intersection of the axes represents the concentration of nickel in the Test solution.Not more than 0.1µg per g is found.
Limit of tin— [NOTE—Use this test for Medium-Chain Triglycerides intended for use in parenteral nutrition.]
Test stock solution andTest solution— Proceed as directed in the test for Limit of chromium.
Tin standard solution— Dissolve 500mg of metallic tin (Sn),accurately weighed,in a mixture of 5mLof water and 25mLof hydrochloric acid,and dilute with water to 1000mL.Immediately before use,dilute 10mLof this solution with dilute hydrochloric acid (2.5in 100)to 1000mL,and then dilute 10mLof the solution so obtained with water to 500mL.This solution contains the equivalent of 0.1µg of tin per g.
Standard solutions— Into each of three 10-mLvolumetric flasks,transfer 4.0mLof Test stock solution,add 1.0,2.0,and 4.0mL,respectively,of Tin standard solution,and dilute with diisobutyl ketone to volume.These solutions contain 0.01µg,0.02µg,and 0.04µg of tin per mL,respectively.
Procedure— Concomitantly determine the absorbances of the Standard solutionsand the Test solutionat least three times each,at the wavelength of maximum absorbance at 286.3nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with a graphite furnace coated inside with palladium carbide and a tin hollow-cathode lamp,using argon as the carrier gas.Record the average of the steady readings for each of the Standard solutionsand the Test solution.Plot the absorbances of the Standard solutionsand the Test solution versus the concentration of added tin.Draw the straight line best fitting the points,and extrapolate the line until it meets the concentration axis.The distance between this point and the intersection of the axes represents the concentration of tin in the Test solution.Not more than 0.1µg per g is found.
Auxiliary Information— Staff Liaison:Elena Gonikberg,Ph.D.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content
USP28–NF23Page 3101
Pharmacopeial Forum:Volume No.30(3)Page 998
Phone Number:1-301-816-8251