Multiple Electrolytes and Dextrose Injection Type 1
»Multiple Electrolytes and Dextrose Injection Type 1is a sterile solution of Dextrose and suitable salts in Water for Injection to provide sodium,potassium,magnesium,and chloride ions.In addition,the salts may provide ions of acetate,or acetate and gluconate,or acetate and phosphate,or phosphate and lactate,or phosphate and sulfate.It contains not less than 90.0percent and not more than 110.0percent of the labeled amounts of sodium (Na),potassium (K),magnesium (Mg),acetate (C2H3O2),gluconate (C6H11O7),phosphate (PO4),lactate (C3H5O3),and sulfate (SO4),not less than 90.0percent and not more than 120.0percent of the labeled amount of chloride (Cl),and not less than 90.0percent and not more than 105.0percent of the labeled amount of dextrose (C6H12O6·H2O).It may contain Hydrochloric Acid or Sodium Hydroxide used to adjust the pH.It contains no antimicrobial agents.
Packaging and storage— Preserve in single-dose glass or plastic containers.Glass containers are preferably of Type Ior Type IIglass.
Labeling— The label states the content of each electrolyte in terms of milliequivalents in a given volume.The label states the total osmolar concentration in mOsmol per liter.When the contents are less than 100mL,the label alternatively may state the total osmolar concentration in mOsmol per mL.
Identification—
A: It responds to the Identificationtest under Dextrose.
B: It responds to the flame tests for Sodium á191ñand Potassium á191ñ,and to the tests for Magnesium á191ñand Chloride á191ñ.
C: Where acetate is purported to be present,the retention time of the acetate peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparationobtained as directed in the Assay for acetate.
D: Where gluconate is purported to be present,the retention time of the gluconate peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparationobtained as directed in the Assay for gluconate.
E: Where phosphate is purported to be present,add 5mLof Injection and 1mLof ammonium molybdate TSto a test tube,and mix:a yellow precipitate,which is soluble in 6Nammonium hydroxide,is formed.
F: Where lactate is purported to be present,the retention time of the lactate peak in the chromatogram of the Assay preparationcorresponds to that of the Standard preparationobtained as directed in the Assay for lactate.
G: Where sulfate is purported to be present,it responds to the barium chloride test for Sulfate á191ñ.
Bacterial endotoxins á85ñ— It contains not more than 0.5USP Endotoxin Unit per mL.
pHá791ñ: between 4.0and 6.5.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for potassium and sodium—
Internal standard solution,Potassium stock solution,Sodium stock solution,Stock standard preparation,and Standard preparation— Prepare as directed in the Assay for potassium and sodiumunder Potassium Chloride in Sodium Chloride Injection.
Assay preparation— Transfer 5.0mLof Injection to a 500-mLvolumetric flask,dilute with Internal standard solutionto volume,and mix.
Procedure— Proceed as directed for Procedurein theAssay for potassium and sodiumunder Potassium Chloride in Sodium Chloride Injection.Calculate the quantity,in mg,of potassium (K)in each mLof the Injection taken by the formula:
C(RU,766/RU,671)(RS,671/RS,766),
in which the terms are as defined therein.Each mg of potassium is equivalent to 0.02558mEq of potassium.Calculate the quantity,in mg,of sodium (Na)in each mLof the Injection taken by the formula:
C(RU,589/RU,671)(RS,671/RS,589),
in which the terms are as defined therein.Each mg of sodium is equivalent to 0.04350mEq of sodium.
Assay for magnesium— [NOTE—Concentrations of the Standard preparations and the Assay preparation may be modified to fit the linear or working range of the atomic absorption spectrophotometer.]
Lanthanum chloride solution,Dilute hydrochloric acid,Blank solution,Magnesium stock solution,and Standard preparations— Prepare as directed in the Assay for magnesiumunder Multiple Electrolytes Injection Type 1.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 20mg (1.65mEq)of magnesium,to a 1000-mLvolumetric flask containing 50.0mLof Lanthanum chloride solution.Dilute the contents of the flask with Dilute hydrochloric acidto volume,and mix.
Procedure— Proceed as directed for Procedurein the Assay for magnesiumunder Multiple Electrolytes Injection Type 1.Calculate the quantity,in µg,of magnesium (Mg)in each mLof the Injection taken by the formula:
1000(C/V),
in which Vis the volume,in mL,of Injection taken to prepare the Assay preparation.
Assay for chloride— Using the Injection,proceed as directed in the Assay for chlorideunder Multiple Electrolytes Injection Type 1.
Assay for acetate (if present)—
Mobile phase,Standard preparation,and Chromatographic system— Prepare as directed in the Assay for acetateunder Multiple Electrolytes Injection Type 1.
Assay preparation— Dilute an accurately measured volume of Injection quantitatively with water to obtain a solution containing about 0.0088mEq of acetate per mL.
Procedure— Proceed as directed for Procedurein the Assay for acetateunder Multiple Electrolytes Injection Type 1.Calculate the quantity,in mEq per liter,of acetate (C2H3O2)in the Injection taken by the formula:
(C/136.08)(L/D)(rU/rS),
in which the terms are as defined therein.
Assay for gluconate (if present)—
Mobile phase— Dissolve 7.0g of calcium acetate in 1900mLof water,and adjust with glacial acetic acid to a pHof 4.5±0.1.Dilute with water to 2000mL,mix,filter through a filter having a porosity of 0.5µm or finer,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).Maintain the Mobile phaseat 70±2at all times.
Standard preparation— Dissolve an accurately weighed quantity of USP Potassium Gluconate RSquantitatively in water to obtain a solution having a known concentration of about 4.6mg per mL.
Resolution solution— Prepare an aqueous solution containing about 5mg each of USP Sodium Lactate RSand USP Potassium Gluconate RSper mL.
Assay preparation— Dilute an accurately measured volume of Injection quantitatively with water,if necessary,to obtain a solution containing about 0.023mEq of gluconate per mL.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a refractive index detector and a 7.8-mm ×30-cm column that contains packing L19in the calcium form and is maintained at 70±2.The flow rate is about 1mLper minute.Condition the column for about 60minutes by pumping Mobile phasethrough it.Chromatograph the Resolution solution,and record the peak responses as directed under Procedure:the resolution between the lactate and gluconate peaks is not less than 4.0.Chromatograph the Standard preparation,and record the peak responses as directed under Procedure:the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mEq per liter,of gluconate (C6H11O7)in the Injection taken by the formula:
(C/234.25)(L/D)(rU/rS),
in which Cis the concentration,in mg per mL,of USP Potassium Gluconate RSin the Standard preparation,234.25is the molecular weight of potassium gluconate,Lis the labeled quantity,in mEq per liter,of gluconate in the Injection,Dis the quantity,in mEq per liter,of gluconate in the Assay preparation,based on the labeled quantity and the extent of dilution,if any,and rUand rSare the gluconate peak responses for the Assay preparationand the Standard preparation,respectively.
Assay for phosphate (if present)—
Ammonium molybdate solution,Hydroquinone solution,Sodium sulfite solution,Standard preparation,and Blank— Prepare as directed in the Assay for phosphateunder Multiple Electrolytes Injection Type 1.
Assay preparation— Transfer an accurately measured volume of Injection,equivalent to about 4mg (0.126mEq)of phosphate,to a 50-mLvolumetric flask,dilute with water to volume,and mix.
Procedure— Proceed as directed for Procedurein the Assay for phosphateunder Multiple Electrolytes Injection Type 1.Calculate the quantity,in mg,of phosphate (PO4)in each mLof the Injection taken by the formula:
50(94.97/136.08)(C/V)(AU/AS),
in which the terms are as defined therein.
Assay for lactate (if present)—
Mobile phase ,Resolution solution,Standard preparation,and Chromatographic system—Prepare as directed in the Assay for lactateunder Multiple Electrolytes Injection Type 2.
Assay preparation— Where the labeled quantity of lactate is greater than 20mEq per liter,dilute an accurately measured volume of Injection quantitatively with water to obtain a solution containing about 0.02mEq of lactate per mL.Where the labeled quantity of lactate is 20mEq or less per liter,use the undiluted Injection as the Assay preparation.
Procedure— Proceed as directed for Procedurein the Assay for lactateunder Multiple Electrolytes Injection Type 2.Calculate the quantity,in mEq per liter,of lactate (C3H5O3)in the Injection taken by the formula:
(C/112.06)(L/D)(rU/rS),
in which the terms are as defined therein.
Assay for sulfate (if present)— Transfer an accurately measured volume of Injection,equivalent to about 120mg (1.22mEq)of sulfate,to a suitable vessel.Dilute if necessary to 200mL,and add 1mLof hydrochloric acid.Heat to boiling,and gradually add,in small portions and while constantly stirring,an excess of hot barium chloride TS(about 8mL).Heat the mixture on a steam bath for 1hour,collect the precipitate of barium sulfate on a tared filtering crucible,wash until free from chloride,dry,ignite,and weigh.The weight of the barium sulfate so obtained,multiplied by 0.4116,represents its equivalent of sulfate (SO4).Each mg of barium sulfate represents 0.004285mEq of sulfate.
Assay for dextrose— Transfer an accurately measured volume of Injection,containing 2to 5g of dextrose,to a 100-mLvolumetric flask.Add 0.2mLof 6Nammonium hydroxide,dilute with water to volume,and mix.Determine the angular rotation in a polarimeter tube at 25(see Optical Rotation á781ñ).The observed rotation,in degrees,multiplied by 1.0425A,in which Ais the ratio 200divided by the length,in mm,of the polarimeter tube employed,represents the weight,in g,of dextrose monohydrate (C6H12O6·H2O)in the volume of Injection taken.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 719
Pharmacopeial Forum:Volume No.30(5)Page 1616
Phone Number:1-301-816-8379