Ubidecarenone
;)
2,5-Cyclohexadiene-1,4-dione,2-[(2E,6E,10E,14E,18E,22E,26E,30E,34E)-3,7,11,15,19,23,27,31,35,39-decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenyl]-5,6-dimethoxy-3-methyl.
2-[(all-E)-3,7,11,15,19,23,27,31,35,39-Decamethyl-2,6,10,14,18,22,26,30,34,38-tetracontadecaenyl)-5,6-dimethoxy-3-methyl-p-benzoquinone [303-98-0].
»Ubidecarenone (Coenzyme Q10)contains not less than 98.0percent and not more than 101.0percent of C59H90O4,calculated on the anhydrous basis.
Packaging and storage—
Preserve in well-closed,light-resistant containers.
Identification—
A:
Infrared Absorption á197Kñ.
B:
Dissolve about 50mg of Ubidecarenone in 1mLof ethyl ether,and add 10mLof dehydrated alcohol.To 2mLof this solution,add 3mLof dehydrated alcohol and 2mLof dimethyl malonate,add 1mLof potassium hydroxide solution (1in 5)dropwise,and mix:a blue color appears.
Water,Method Iá921ñ:
not more than 0.2%.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method IIá231ñ:
0.002%.
Chromatographic purity—
TEST1:COENZYMESQ7,Q8,Q9,Q11AND RELATED IMPURITIES—
Mobile phase—
Proceed as directed in the Assay.
Chromatographic system—
Proceed as directed in the Assay.To evaluate the system suitability requirements,use the System suitability preparation,as prepared in the Assay.
Standard solution and Test solution—
Use the Standard preparationand the Assay preparation,as prepared in the Assay.
Procedure—
Proceed as directed in the Assay,measure all the peak areas,and calculate the percentage of impurities in the portion of Ubidecarenone taken by the formula:
100(ri/rs),
in which riis the sum of all peak responses,other than that for ubidecarenone,obtained from the Test solution;and rsis the sum of all peak responses.Not more than 1.0%is found.
TEST2:UBIDECARENONE(2Z)-ISOMER AND RELATED IMPURITIES—
Mobile phase—
Prepare a filtered and degassed mixture of n-hexane and ethyl acetate (97:3).
System suitability solution—
Prepare a solution of USP Ubidecarenone for System Suitability RSin n-hexane having a concentration of about 1mg per mL.
Test solution—
Prepare a solution of Ubidecarenone in n-hexane having a concentration of about 1mg per mL.
Chromatographic system—
The liquid chromatograph is equipped with a 275-nm detector and a 4.6-mm ×25-cm column that contains packing L3.The flow rate is about 2.0mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times are about 0.85for ubidecarenone (2Z)-isomer and 1.0for ubidecarenone;and the resolution,R,between ubidecarenone (2Z)-isomer and ubidecarenone is not less than 1.5.
Procedure—
Inject a volume of the Test solution(about 20µL)into the chromatograph,record the chromatogram,and measure all the peak responses.Calculate the percentage of impurities in the portion of Ubidecarenone taken by the formula:
100(ri/rs),
in which riis the sum of all peak responses,other than that for ubidecarenone;and rsis the sum of all peak responses.Not more than 1.0%is found.
Calculate the percentage of total impurities as the sum of the percentages obtained by Test 1and Test 2:not more than 1.5%of total impurities is found.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of methanol and dehydrated alcohol (13:7).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability preparation—
Dissolve accurately weighed quantities of USP Ubidecarenone RSand coenzyme Q9in dehydrated alcohol,heating at about 50
for 2minutes if necessary,to obtain a solution having known concentrations of about 0.5mg of each per mL.
for 2minutes if necessary,to obtain a solution having known concentrations of about 0.5mg of each per mL.
Standard preparation—
Dissolve an accurately weighed quantity of USP Ubidecarenone RSin dehydrated alcohol,heating at about 50for 2minutes if necessary,to obtain a solution having a known concentration of about 1.0mg per mL.
for 2minutes if necessary,to obtain a solution having a known concentration of about 1.0mg per mL.
Assay preparation—
Transfer about 50mg of Ubidecarenone,accurately weighed,to a 50-mLvolumetric flask,dissolve in dehydrated alcohol,heating at about 50for 2minutes if necessary,cool,dilute with dehydrated alcohol to volume,and mix.
for 2minutes if necessary,cool,dilute with dehydrated alcohol to volume,and mix.
Chromatographic system (see Chromatography á621ñ)—
The liquid chromatograph is equipped with a 275-nm detector and a 5-mm ×15-cm column that contains packing L1,and is maintained at a temperature of 35.The flow rate is adjusted to obtain a retention time of about 11minutes.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.75for coenzyme Q9and 1.0for ubidecarenone;the resolution,R,between coenzyme Q9and ubidecarenone is not less than 4;and the relative standard deviation for replicate injections is not more than 0.8%.
.The flow rate is adjusted to obtain a retention time of about 11minutes.Chromatograph the System suitability preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.75for coenzyme Q9and 1.0for ubidecarenone;the resolution,R,between coenzyme Q9and ubidecarenone is not less than 4;and the relative standard deviation for replicate injections is not more than 0.8%.
Procedure—
Separately inject equal volumes (about 5µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C59H90O4in the portion of Ubidecarenone taken by the formula:
50C(rU/rS),
in which Cis the concentration,in mg per mL,of USP Ubidecarenone RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(DSN)Dietary Supplements:Non-Botanicals
USP28–NF23Page 2132
Pharmacopeial Forum:Volume No.26(6)Page 1601
Phone Number:1-301-816-8389