Trace Elements Injection
»Trace Elements Injection is a sterile solution in Water for Injection of two or more of the following:Zinc Chloride or Zinc Sulfate,Cupric Chloride or Cupric Sulfate,Chromic Chloride,Manganese Chloride or Manganese Sulfate,Selenious Acid,Sodium Iodide,and Ammonium Molybdate.It contains not less than 90.0percent and not more than 110.0percent of the labeled amounts of zinc (Zn),copper (Cu),chromium (Cr),manganese (Mn),selenium (Se),iodine (I),and molybdenum (Mo).
Packaging and storage— Preserve in single-dose or in multiple-dose containers,preferably of Type Ior Type IIglass.
Labeling— Label the Injection to specify that it is to be diluted to the appropriate strength with Sterile Water for Injection or other suitable fluid prior to administration.The label shows by an appropriate number juxtaposed to the official name,the number of trace elements contained in the Injection according to the following:zinc and copper (2),and then cumulatively,chromium (3),manganese (4),selenium (5),iodine (6),and molybdenum (7).Other combinations are indicated separately by citing the number of trace elements contained in each followed by an asterisk that is repeated with the list of labeled ingredients.Label the Injection for its contents of zinc chloride (ZnCl2),zinc sulfate (ZnSO4·7H2O),cupric chloride (CuCl2),cupric sulfate (CuSO4),chromic chloride (CrCl2),manganese chloride (MnCl2),manganese sulfate (MnSO4),selenious acid (H2SeO3),sodium iodide (NaI),and ammonium molybdate [(NH4)Mo7·4H2O],and for elemental zinc (Zn),copper (Cu),chromium (Cr),manganese (Mn),selenium (Se),iodine (I),and molybdenum (Mo),as appropriate in relation to the ingredients claimed to be present.
Identification—
A: The Assay preparationprepared as directed in the Assay for zinc,the Assay for copper,the Assay for chromium,the Assay for manganese,the Assay for selenium,and the Assay for molybdenum,as appropriate,based on the elements claimed in the labeling to be present,exhibit maximum absorption at the relevant wavelengths specified when tested as directed for the Proceduresin the respective Assays.
B: If iodine is claimed in the labeling to be present,the retention time of the iodine peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparationas obtained in the Assay for iodine.
Pyrogen— When diluted with Sodium Chloride Injection so that each mLcontains not more than 20µg of zinc,20µg of copper,0.1µg of chromium,4µg of manganese,4µg of selenium,5µg of iodine,or 5µg of molybdenum,it meets the requirements of the Pyrogen Test á151ñ.
pHá791ñ: between 1.5and 3.5.
Particulate matter á788ñ: meets the requirements.
Other requirements— It meets the requirements under Injection á1ñ.
Assay for zinc—
Standard preparations— Prepare as directed in the Assayunder Zinc Chloride Injection.
Assay preparation— Using the Injection,proceed as directed for Assay preparationin the Assayunder Zinc Chloride Injection.
Procedure— Proceed as directed for Procedurein the Assayunder Zinc Chloride Injection.Calculate the quantity,in µg,of zinc (Zn)in each mLof the Injection taken by the formula:
5C/V,
in which Cis the concentration,in µg per mL,of zinc in the Assay preparation,and Vis the volume,in mL,of Injection taken.
Assay for copper—
Sodium chloride solution ,Copper stock solution,and Standard preparations—Prepare as directed in the Assayunder Cupric Chloride Injection.
Assay preparation— Using the Injection,proceed as directed for the Assay preparationin the Assayunder Cupric Chloride Injection.
Procedure— Proceed as directed for Procedurein the Assayunder Cupric Chloride Injection.Calculate the quantity,in mg,of copper (Cu)in each mLof the Injection taken by the formula:
2C/3V,
in which Cis the concentration,in µg per mL,of copper in the Assay preparation,and Vis the volume,in mL,of Injection taken.
Assay for chromium (if present)—
INJECTIONS CONTAINING 3µg OR MORE OF Cr PERmL—
Sodium chloride solution ,Chromium stock solution,Standard preparations,Assay preparation,and Procedure—Proceed as directed in the Assayunder Chromic Chloride Injection.Calculate the quantity,in µg,of chromium (Cr)in each mLof the Injection taken by the formula:
25C/V,
in which Cis the concentration,in µg per mL,of chromium in the Assay preparation,and Vis the volume,in mL,of Injection taken.
INJECTIONS CONTAINING LESS THAN 3µg OF Cr PERmL—
Sodium chloride solution and Chromium stock solution—Proceed as directed in the Assayunder Chromium Chloride Injection.
Standard preparations— Prepare as directed in the Assayunder Chromic Chloride Injection.If the Injection is not labeled as containing sodium chloride,omit the addition of the Chromium Chloride Injection.
Assay preparation— Use the undiluted Injection.
Procedure— Proceed as directed for Procedurein the Assayunder Chromic Chloride Injection.Calculate the quantity,in µg,of chromium (Cr)in each mLof the Injection taken by the formula:
25C/V,
in which Cis the concentration,in µg per mL,of chromium in the Assay preparation,and Vis the volume,in mL,of Injection taken.
Assay for manganese (if present)—
Sodium chloride solution ,Manganese stock solution,and Standard preparations—Prepare as directed in the Assayunder Manganese Chloride Injection.
Assay preparation— Using the Injection,proceed as directed for the Assay preparationin the Assayunder Manganese Chloride Injection.
Procedure— Proceed as directed for Procedurein the Assayunder Manganese Chloride Injection.Calculate the quantity,in µg,of manganese (Mn)in each mLof the Injection taken by the formula:
0.5C/V,
in which Cis the concentration,in µg per mL,of manganese in the Assay preparation,and Vis the volume,in mL,of Injection taken.
Assay for selenium (if present)—
Selenium stock solution and Standard preparations—Prepare as directed in the Assayunder Selenious Acid Injection.
Assay preparation— Using the Injection,proceed as directed for Assay preparationin the Assayunder Selenious Acid Injection.
Procedure— Proceed as directed for Procedurein the Assayunder Selenious Acid Injection.Calculate the quantity,in mg,of selenium (Se)in each mLof the Injection taken by the formula:
LC/D,
in which Lis the labeled quantity,in mg per mL,of selenium in the Injection taken,Cis the concentration,in µg per mL,in the Assay preparation,and Dis the concentration,in µg of selenium per mL,of the Assay preparationon the basis of the labeled quantity in the Injection and the extent of dilution.
Assay for iodine (if present)—
Mobile phase— Prepare a suitable mixture of 0.05Mdibasic sodium phosphate,0.0025Mcetyltrimethylammonium chloride (prepared by diluting 3.20g of a 25%solution of cetyltrimethylammonium chloride with water to 1000mL),and acetonitrile (45:25:25).Filter this mixture through a suitable filter of 0.5µm or finer porosity,adjust with phosphoric acid to a pHof 6.8±0.1,and mix.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparations— Transfer about 52mg of potassium iodide,accurately weighed,to a 250-mLvolumetric flask,dissolve in and dilute with water to volume,and mix.Transfer 5.0mLof this solution to a 200-mLvolumetric flask,dilute with water to volume,and mix.This solution contains about 5.2µg of potassium iodide per mL(equivalent to about 4µg of iodine per mL).
Assay preparation— Dilute an accurately measured volume of Injection quantitatively with water to obtain a solution containing about 4µg of iodine per mL.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 226-nm detector,a precolumn containing packing L3,and a 4.6×25-cm column that contains packing L1.The flow rate is about 2.5mLper minute.[NOTE—Equilibrate the column with Mobile phase recirculating at a rate of about 1mLper minute for at least 12hours before use.]Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the tailing factor for the iodine peak is not more than 2,and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the areas for the iodine peaks.Calculate the quantity,in µg,of iodine in each mLof the Injection taken by the formula:
(126.9/166.0)(CL/D),
in which 126.9is the atomic weight of iodine,166.0is the molecular weight of potassium iodide,Cis the concentration,in µg per mL,of potassium iodide,calculated on the dried basis,in the Standard preparation,Lis the labeled concentration,in µg per mL,of iodine in the Injection,and Dis the concentration,in µg per mL,of iodine in the Assay preparationbased on the labeled concentration and the extent of dilution.
Assay for molybdenum (if present)—
Ammonium hydroxide diluent ,Sodium sulfate solution,Molybdenum stock solution,and Standard preparations—Prepare as directed in the Assayunder Ammonium Molybdate Injection.
Assay preparation— Using the Injection,proceed as directed for the Assay preparationin the Assayunder Ammonium Molybdate Injection.
Procedure— Proceed as directed for Procedurein the Assayunder Ammonium Molybdate Injection.Calculate the quantity,in µg,of molybdenum (Mo)in each mLof the Injection taken by the formula:
25C/V,
in which Cis the concentration,in µg per mL,of molybdenum in the Assay preparation,and Vis the volume,in mL,of Injection taken.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 726
Phone Number:1-301-816-8379