Packaging and storage—
Preserve in single-dose or in multiple-dose containers, preferably of Type I or Type II glass.
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 (CrCl3), 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—
B:
If iodine is claimed in the labeling to be present, the retention time of the iodine peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation as obtained in the Assay for iodine.
Pyrogen—
When diluted with Sodium Chloride Injection so that each mL contains not more than 20 µg of zinc, 20 µg of copper, 0.1 µg of chromium, 4 µg of manganese, 4 µg of selenium, 5 µg of iodine, or 5 µg of molybdenum, it meets the requirements of the
Pyrogen Test 
151
.
Other requirements—
It meets the requirements under
Injection 1.
Assay for zinc—
Procedure—
Proceed as directed for
Procedure in the
Assay under
Zinc Chloride Injection. Calculate the quantity, in µg, of zinc (Zn) in each mL of the Injection taken by the formula:
5C/V,
in which
C is the concentration, in µg per mL, of zinc in the
Assay preparation, and
V is the volume, in mL, of Injection taken.
Assay for copper—
Procedure—
Proceed as directed for
Procedure in the
Assay under
Cupric Chloride Injection. Calculate the quantity, in mg, of copper (Cu) in each mL of the Injection taken by the formula:
2C/3V,
in which
C is the concentration, in µg per mL, of copper in the
Assay preparation, and
V is the volume, in mL, of Injection taken.
Assay for chromium (if present)—
INJECTIONS CONTAINING
3 µg OR MORE OF Cr PER mL—
Sodium chloride solution, Chromium stock solution, Standard preparations, Assay preparation, and Procedure—
Proceed as directed in the
Assay under
Chromic Chloride Injection. Calculate the quantity, in µg, of chromium (Cr) in each mL of the Injection taken by the formula:
25C/V,
in which
C is the concentration, in µg per mL, of chromium in the
Assay preparation, and
V is the volume, in mL, of Injection taken.
INJECTIONS CONTAINING LESS THAN
3 µg OF Cr PER mL—
Assay preparation—
Use the undiluted Injection.
Procedure—
Proceed as directed for
Procedure in the
Assay under
Chromic Chloride Injection. Calculate the quantity, in µg, of chromium (Cr) in each mL of the Injection taken by the formula:
25C/V,
in which
C is the concentration, in µg per mL, of chromium in the
Assay preparation, and
V is the volume, in mL, of Injection taken.
Assay for manganese (if present)—
Procedure—
Proceed as directed for
Procedure in the
Assay under
Manganese Chloride Injection. Calculate the quantity, in µg, of manganese (Mn) in each mL of the Injection taken by the formula:
0.5C/V,
in which
C is the concentration, in µg per mL, of manganese in the
Assay preparation, and
V is the volume, in mL, of Injection taken.
Assay for selenium (if present)—
Procedure—
Proceed as directed for
Procedure in the
Assay under
Selenious Acid Injection. Calculate the quantity, in mg, of selenium (Se) in each mL of the Injection taken by the formula:
LC/D,
in which
L is the labeled quantity, in mg per mL, of selenium in the Injection taken,
C is the concentration, in µg per mL, in the
Assay preparation, and
D is the concentration, in µg of selenium per mL, of the
Assay preparation on 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 0.05 M dibasic sodium phosphate, 0.0025 M cetyltrimethylammonium chloride (prepared by diluting 3.20 g of a 25% solution of cetyltrimethylammonium chloride with water to 1000 mL), and acetonitrile (45:25:25). Filter this mixture through a suitable filter of 0.5 µm or finer porosity, adjust with phosphoric acid to a pH of 6.8 ± 0.1, and mix. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparations—
Transfer about 52 mg of potassium iodide, accurately weighed, to a 250-mL volumetric flask, dissolve in and dilute with water to volume, and mix. Transfer 5.0 mL of this solution to a 200-mL volumetric flask, dilute with water to volume, and mix. This solution contains about 5.2 µg of potassium iodide per mL (equivalent to about 4 µg of iodine per mL).
Assay preparation—
Dilute an accurately measured volume of Injection quantitatively with water to obtain a solution containing about 4 µg of iodine per mL.
Chromatographic system
(see
Chromatography 621)—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 2.5 mL per minute.
[NOTE—Equilibrate the column with
Mobile phase recirculating at a rate of about 1 mL per minute for at least 12 hours 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 20 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the iodine peaks. Calculate the quantity, in µg, of iodine in each mL of the Injection taken by the formula:
(126.9 / 166.0)(CL / D),
in which 126.9 is the atomic weight of iodine, 166.0 is the molecular weight of potassium iodide,
C is the concentration, in µg per mL, of potassium iodide, calculated on the dried basis, in the
Standard preparation,
L is the labeled concentration, in µg per mL, of iodine in the Injection, and
D is the concentration, in µg per mL, of iodine in the
Assay preparation based 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
Assay under
Ammonium Molybdate Injection.
Procedure—
Proceed as directed for
Procedure in the
Assay under
Ammonium Molybdate Injection. Calculate the quantity, in µg, of molybdenum (Mo) in each mL of the Injection taken by the formula:
25C / V,
in which
C is the concentration, in µg per mL, of molybdenum in the
Assay preparation, and
V is the volume, in mL, of Injection taken.
