Mangafodipir Trisodium
C22H27MnN4Na3O14P2
![]() ![]() ![]() ![]() ![]() Trisodium trihydrogen (OC-6-13)-[[N,N¢-1,2-ethanediylbis[N-[[3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinyl]methyl]glycinato]](8-)] manganate(6-). Trisodium trihydrogen (OC-6-13)-[[N,N¢-ethylenebis[N-[[3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridyl]methyl]glycine] 5,5¢-bis(phosphato)](8-)]manganate(6-) ![]() ![]() ![]() » Mangafodipir Trisodium contains not less than 97.0 percent and not more than 103.0 percent of C22H27MnN4Na3O14P2, calculated on the anhydrous basis.
Packaging and storage
Preserve in well-closed containers. Store in a cold place.
USP Reference standards
![]() ![]() USP Endotoxin RS. USP Mangafodipir Related Compound A RS ![]() USP Mangafodipir Related Compound B RS. USP Mangafodipir Related Compound C RS ![]() USP Mangafodipir Trisodium RS ![]()
Identification
Microbial enumeration tests
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Bacterial endotoxins
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pH
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Water, Method I
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Limit of residual solvents
Internal standard solution
Transfer 600 µL of methyl ethyl ketone to a 100-mL volumetric flask, dilute with water to volume, and mix to obtain a solution having a concentration of about 5 mg per mL. Transfer 2 mL of this solution to a 100-mL volumetric flask, dilute with water to volume, and mix to obtain a solution having a known concentration of about 0.1 mg per mL.
Standard stock solution
Transfer about 1 g of dehydrated alcohol and 1 g of acetone, both accurately weighed, to a 100-mL volumetric flask, and dilute with water to volume. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, dilute with water to volume, and mix to obtain a solution having a known concentration of about 1 mg each of alcohol and acetone per mL.
Standard solutions
Transfer 10.0 mL of Internal standard solution to each of four 100-mL volumetric flasks. Separately add 0 mL, 1.0 mL, 5.0 mL, and 10.0 mL of Standard stock solution to the volumetric flasks, and dilute each with water to volume to obtain solutions having known concentrations of 0.0 µg per mL and about 10 µg per mL, 50 µg per mL, and 100 µg per mL each of alcohol and acetone, respectively. Add 7.0 mL of each Standard solution to separate headspace sample vials, and cap.
Test solution
Transfer about 1 g of Mangafodipir Trisodium, accurately weighed, to a sample vial, add 7.0 mL of the Standard solution having a concentration of 0.0 µg per mL, cap, and swirl to dissolve.
Chromatographic system (see Chromatography
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Procedure
Separately inject equal volumes (about 1 mL) of the gaseous headspace of each of the Standard solutions and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentages (w/w) of alcohol and acetone in the portion of Mangafodipir Trisodium taken by the formula:
(7/10,000)(C/W)
in which C is the concentration, in µg per mL, of alcohol or acetone in the Test solution, as determined from the relevant standard response line; and W is the weight, in g, of Mangafodipir Trisodium taken: not more than 0.1% of alcohol is found; and not more than 0.01% of acetone is found, both calculated on the anhydrous basis.
Limit of free manganese and free fodipir
Ascorbic acid solution
Dissolve 0.5 g of ascorbic acid in 10 mL of water.
Manganese solution
Transfer about 3.6 g of manganese chloride, accurately weighed, to a 1000-mL volumetric flask, dissolve in and dilute with 0.1 N hydrochloric acid to volume, and mix. Transfer 100.0 mL of this solution to a 500-mL volumetric flask, dilute with water to volume, and mix.
Edetate titrant solution
Transfer about 37 g of edetate disodium, accurately weighed, to a 1000-mL volumetric flask, dilute with water to volume, and mix. Transfer 36 mL of this solution to a 1000-mL volumetric flask, dilute with water to volume, and mix to obtain a solution having a concentration of 0.0036 moles per L.
standardization of 0.0036 m edetate titrant solution
Accurately weigh about 200 mg of chelometric standard calcium carbonate, previously dried at 110
![]() (5/100.09)(W)/(100V)
in which 100.09 is the molecular weight of calcium carbonate; W is the weight, in mg, of the calcium carbonate taken; and V is the final titration volume, in mL, of Edetate titrant solution.
Procedure
Transfer about 1 g of Mangafodipir Trisodium, accurately weighed, to a suitable beaker, add about 100 mL of water, 1.0 mL of Ascorbic acid solution, 10 mL of ammoniaammonium chloride buffer TS, 0.1 mL of eriochrome black TS, and 1.0 mL of Manganese solution, and record the color. If the color is yellow to green, add additional 1.0-mL increments of Manganese solution until the color is red. Record the volume added. Titrate with the Edetate titrant solution, determining the endpoint photometrically. Perform a blank determination, and make any necessary correction (see Titrimetry
![]() ![]() 5.49V(M/W)
in which V is the volume, in mL, of the Edetate titrant solution; M is the molarity of the Edetate titrant solution; and W is the weight, in g, of Mangafodipir Trisodium taken. Calculate the percentage of free fodipir in the portion of Mangafodipir Trisodium taken by the formula:
63.85V(M/W)
in which V, M, and W are as defined herein: not more than 0.03% of free manganese is found; and not more than 0.5% of free fodipir is found, both calculated on the anhydrous basis.
Related compounds
Ascorbic acid solution
Dissolve 0.4 g of ascorbic acid in 100 mL of water.
Phosphate buffer
Prepare as directed in the Assay.
Mobile phase
Prepare as directed in the Assay. [noteIncreasing the proportion of acetonitrile will decrease the retention times.]
System suitability stock solution
Prepare as directed for Standard stock preparation in the Assay.
System suitability solution 1
Prepare a solution of USP Mangafodipir Trisodium RS having a known concentration of about 4.0 mg per mL. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, add 5.0 mL of System suitability stock solution, 5.0 mL of Phosphate buffer, and 5.0 mL of Ascorbic acid solution. Dilute with nitrogen-purged water to volume, and mix to obtain a solution having a concentration of about 0.4 mg of USP Mangafodipir Trisodium RS, and about 0.01 mg each of USP Mangafodipir Related Compound A RS and USP Mangafodipir Related Compound B RS per mL. [noteStore in a refrigerator and under nitrogen to avoid excessive exposure to heat, air, and light.]
System suitability solution 2
Transfer about 10 mg of USP Mangafodipir Related Compound C RS to a 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, and add 5.0 mL of Phosphate buffer.
Test solution
Transfer an accurately weighed quantity of Mangafodipir Trisodium, equivalent to about 100 mg of mangafodipir trisodium, to a 50-mL volumetric flask, dilute with water to volume, and mix. Transfer 10.0 mL of this solution to a second 50-mL volumetric flask, add 5.0 mL of Phosphate buffer, dilute with water to volume, and mix. [noteStore in a refrigerator and under nitrogen to avoid excessive exposure to heat, air, and light.]
Chromatographic system (see Chromatography
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Procedure
Inject about 10 µL of the Test solution into the chromatograph, record the chromatogram, and measure the areas for all the major peaks. The relative retention times for ascorbic acid, mangafodipir related compound A, Mn(II)-5-methyl dipyridoxal monophosphate (Mn(II)-5-methyl DPMP) if present, mangafodipir related compound C, mangafodipir related compound B, and mangafodipir are about 0.1, 0.3, 0.4, 0.6, 0.8, and 1.0, respectively. Calculate the percentages of mangafodipir related compound A, mangafodipir related compound B, mangafodipir related compound C, and Mn(II)-5-methyl DPMP in the portion of Mangafodipir Trisodium taken by the formula:
100(ri / rs)
in which ri is the peak area of each impurity; and rs is the sum of the areas of all of the peaks: not more than 0.5% each of mangafodipir related compound A and mangafodipir related compound B is found; not more than 0.6% of mangafodipir related compound C is found; not more than 0.3% of Mn(II)-5-methyl DPMP is found; not more than 0.3% of any other impurity is found; not more than a total of 0.5% of other impurities is found; and not more than a total of 2.0% of impurities is found.
Assay
Phosphate buffer
Transfer about 26.8 g of dibasic sodium phosphate to a 1000-mL volumetric flask, add 900 mL of water, and adjust with 1 N sodium hydroxide or 1 N hydrochloric acid to a pH of about 8.0. Dilute with water to volume, filter, and degas.
Mobile phase
Transfer about 0.61 g of boric acid and 9.2 g of tetrabutylammonium hydrogen sulfate to a 1000-mL volumetric flask, add 640 mL water, and mix. Adjust with 3 N sodium hydroxide to a pH of about 9.3, add 250 mL of acetonitrile, dilute with water to volume, and mix. Adjust with 3 N hydrochloric acid or 3 N sodium hydroxide to a pH of about 10.5, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography
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Standard stock preparation
Transfer about 10 mg each of USP Mangafodipir Related Compound A RS and USP Mangafodipir Related Compound B RS, both accurately weighed, to a 100-mL volumetric flask, dilute with water to volume, and mix.
Standard preparation
Transfer about 100 mg of USP Mangafodipir Trisodium RS to a 50-mL volumetric flask, dilute with water to volume, and mix. Transfer 10.0 mL of this solution to a 50-mL volumetric flask, add 5.0 mL of Standard stock preparation and 5.0 mL of Phosphate buffer, dilute with water to volume, and mix. [noteStore in a refrigerator and under nitrogen to avoid exposure to excessive heat, air, or light.]
Assay preparation
Transfer an accurately measured quantity of Mangafodipir Trisodium, equivalent to about 100 mg of mangafodipir trisodium, to a 50-mL volumetric flask, dilute with water to volume, and mix. Transfer 10.0 mL of this solution to a 50-mL volumetric flask, add 5.0 mL of Phosphate buffer, dilute with water to volume, and mix. [noteStore in a refrigerator and under nitrogen to avoid exposure to excessive heat, air, or light.]
Chromatographic system (see Chromatography
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Procedure
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of C22H27MnN4Na3O14P2 in the portion of Mangafodipir Trisodium taken by the formula:
25,000(C/W)(rU / rS)
in which C is the concentration, in mg per mL, of USP Mangafodipir Trisodium RS in the Standard preparation; W is the weight, in mg, of the Mangafodipir Trisodium taken; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP32NF27 Page 2842
Pharmacopeial Forum: Volume No. 31(6) Page 1650
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