Calcium Gluconate
;)
D-Gluconic acid,calcium salt (2:1).
Calcium D-gluconate (1:2) [299-28-5].
Monohydrate 448.39
»Calcium Gluconate is anhydrous or contains one molecule of water of hydration.The anhydrous form contains not less than 98.0percent and not more than 102.0percent of C12H22CaO14,calculated on the dried basis.The monohydrate form contains not less than 99.0percent and not more than 101.0percent of C12H22CaO14·H2Owhere labeled as intended for use in preparing injectable dosage forms,and not less than 98.5percent and not more than 102.0percent of C12H22CaO14·H2Owhere labeled as not intended for use in preparing injectable dosage forms.
Packaging and storage—
Preserve in well-closed containers.
Labeling—
Label it to indicate whether it is the anhydrous or the monohydrate.Where the quantity of calcium gluconate is indicated in the labeling of any preparation containing Calcium Gluconate,this shall be understood to be in terms of anhydrous calcium gluconate (C12H22CaO14).Calcium Gluconate intended for use in preparing injectable dosage forms is so labeled.Calcium Gluconate not intended for use in preparing injectable dosage forms is so labeled;in addition,it may be labeled also as intended for use in preparing oral dosage forms.
Identification—
A:
Asolution (1in 50)responds to the test for Calcium á191ñ.
B:
Dissolve a quantity of it in water to obtain a test solution containing 10mg per mL,heating in a water bath at 60
if necessary.Similarly,prepare a Standard solution of USP Potassium Gluconate RSin water containing 10mg per mL.Apply separate 5-µLportions of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel,and allow to dry.Develop the chromatogram in a solvent system consisting of a mixture of alcohol,water,ammonium hydroxide,and ethyl acetate (50:30:10:10)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,and dry at 110for 20minutes.Allow to cool,spray with a spray reagent prepared as follows.Dissolve 2.5g of ammonium molybdate in about 50mLof 2Nsulfuric acid in a 100-mLvolumetric flask,add 1.0g of ceric sulfate,swirl to dissolve,dilute with 2Nsulfuric acid to volume,and mix.Heat the plate at 110for about 10minutes:the principal spot obtained from the test solution corresponds in color,size,and RFvalue to that obtained from the Standard solution.
if necessary.Similarly,prepare a Standard solution of USP Potassium Gluconate RSin water containing 10mg per mL.Apply separate 5-µLportions of the test solution and the Standard solution to a suitable thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel,and allow to dry.Develop the chromatogram in a solvent system consisting of a mixture of alcohol,water,ammonium hydroxide,and ethyl acetate (50:30:10:10)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the chamber,and dry at 110for 20minutes.Allow to cool,spray with a spray reagent prepared as follows.Dissolve 2.5g of ammonium molybdate in about 50mLof 2Nsulfuric acid in a 100-mLvolumetric flask,add 1.0g of ceric sulfate,swirl to dissolve,dilute with 2Nsulfuric acid to volume,and mix.Heat the plate at 110for about 10minutes:the principal spot obtained from the test solution corresponds in color,size,and RFvalue to that obtained from the Standard solution.
Loss on drying á731ñ—
Dry it at 105for 16hours:the anhydrous form loses not more than 3.0%of its weight;the monohydrate form,where labeled as intended for use in preparing injectable dosage forms,loses not more than 1.0%of its weight,and where labeled as not intended for use in preparing injectable dosage forms loses not more than 2.0%of its weight.
for 16hours:the anhydrous form loses not more than 3.0%of its weight;the monohydrate form,where labeled as intended for use in preparing injectable dosage forms,loses not more than 1.0%of its weight,and where labeled as not intended for use in preparing injectable dosage forms loses not more than 2.0%of its weight.
Chloride á221ñ—
A1.0-g portion shows no more chloride than corresponds to 0.07mLof 0.020Nhydrochloric acid (0.005%).Where it is labeled as not intended for use in the preparation of injectable dosage forms,a 1.0-g portion shows no more chloride than corresponds to 1mLof 0.020Nhydrochloric acid (0.07%).
Limit of oxalate—
[NOTE—Use deionized water where water is indicated.]
Mobile phase—
Prepare a solution in water that is 0.0017Mwith respect to sodium bicarbonate and 0.0018Mwith respect to sodium carbonate.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Suppressor regeneration solution—
Prepare a solution in water that is 0.0125Mwith respect to sulfuric acid.
Dilute hydrochloric acid—
Dilute 1mLof hydrochloric acid with water to obtain 1200mLof solution.
Standard preparation—
Dissolve an accurately weighed quantity of sodium oxalate in Dilute hydrochloric acidto obtain a solution having a known concentration of about 1.5µg per mL.
Test preparation—
Transfer 500mg of Calcium Gluconate to a 25-mLvolumetric flask,dissolve in Dilute hydrochloric acid,sonicating if necessary,dilute with Dilute hydrochloric acidto volume,and mix.
Chromatographic system (seeChromatography á621ñ)—
The ion chromatograph is equipped with a conductance detector,a 4-mm ×5-cm guard column that contains 15-µm packing L12,a 4-mm ×25-cm analytical column that contains 15-µm packing L12,and a micromembrane anion suppressor column,connected in series with the guard and analytical columns.The anion suppressor column is equipped with a micromembrane that separates the Mobile phasefrom the Suppressor regeneration solutionflowing countercurrent to the Mobile phaseat a rate of about 7mLper minute.Condition the system for about 15minutes with Mobile phase,using a flow rate of about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the column efficiency determined from the analyte peak is not less than 2500theoretical plates;the tailing factor is not more than 1.2;and 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 Test preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the percentage of oxalate in the specimen taken by the formula:
(88.03/134.00)(0.005C)(rU/rS),
in which 88.03and 134.00are the molecular weights of oxalate and sodium oxalate,respectively;Cis the concentration,in µg per mL,of sodium oxalate in the Standard preparation;and rUand rSare the oxalate peak responses obtained from the Test preparationand the Standard preparation,respectively:not more than 0.01%is found.[NOTE—Calcium Gluconate labeled as not intended for use in the preparation of injectable dosage forms is exempt from this requirement.]
Limit of phosphate—
To 10.0g add 90mLof hot water,(70to 80),and heat to boiling,with swirling,for 10seconds to obtain a clear solution.Dilute 1mLof this hot solution with water to obtain 100mLof solution (test solution).Dilute 1.0mLof a solution containing 0.716mg of monobasic potassium phosphate per mLwith water to obtain 100mLof solution.To 2.0mLof this solution add 98mLof water (Standard solution).To the test solution and the Standard solution add 4mLof sulfomolybdic acid TS,and mix.To both solutions add 0.1mLof a freshly prepared mixture of 3Nhydrochloric acid and stronger acid stannous chloride TS(10:1),and mix.After 10minutes any color observed in the test solution is not more intense than that obtained from the Standard solution (0.01%).[NOTE—Calcium Gluconate labeled as not intended for use in the preparation of injectable dosage forms is exempt from this requirement.]
to 80),and heat to boiling,with swirling,for 10seconds to obtain a clear solution.Dilute 1mLof this hot solution with water to obtain 100mLof solution (test solution).Dilute 1.0mLof a solution containing 0.716mg of monobasic potassium phosphate per mLwith water to obtain 100mLof solution.To 2.0mLof this solution add 98mLof water (Standard solution).To the test solution and the Standard solution add 4mLof sulfomolybdic acid TS,and mix.To both solutions add 0.1mLof a freshly prepared mixture of 3Nhydrochloric acid and stronger acid stannous chloride TS(10:1),and mix.After 10minutes any color observed in the test solution is not more intense than that obtained from the Standard solution (0.01%).[NOTE—Calcium Gluconate labeled as not intended for use in the preparation of injectable dosage forms is exempt from this requirement.]
Sulfate á221ñ—
A2.0-g portion dissolved in boiling water shows no more sulfate than corresponds to 0.1mLof 0.020Nsulfuric acid (0.005%).Where it is labeled as not intended for use in the preparation of injectable dosage forms,a 2.0-g portion dissolved in boiling water shows no more sulfate than corresponds to 1mLof 0.020Nsulfuric acid (0.05%).
Arsenic,Method Iá211ñ—
Dissolve 1.0g in a mixture of 10mLof hydrochloric acid and 20mLof water,and dilute with water to 55mL:the resulting solution meets the requirements of the test,the addition of 20mLof 7Nsulfuric acid specified under Procedurebeing omitted.The limit is 3ppm.
Heavy metals,Method IIá231ñ:
0.001%.[NOTE—Where Calcium Gluconate is labeled as not intended for use in the preparation of injectable dosage forms,the limit is 0.002%.]
Limit of magnesium and alkali metals—
Dissolve completely 1.0g in 100mLof boiling water,add 10mLof ammonium chloride TS,1mLof ammonium hydroxide,and 50mLof hot,maintained at 70to 80,ammonium oxalate TS.Allow to stand for 4hours,dilute with water to 200mL,and filter.Evaporate 100mLof the filtrate to dryness,and ignite to constant weight.The weight of the residue does not exceed 2mg (0.4%).[NOTE—Calcium Gluconate labeled as not intended for use in preparing injectable dosage forms is exempt from this requirement.]
to 80,ammonium oxalate TS.Allow to stand for 4hours,dilute with water to 200mL,and filter.Evaporate 100mLof the filtrate to dryness,and ignite to constant weight.The weight of the residue does not exceed 2mg (0.4%).[NOTE—Calcium Gluconate labeled as not intended for use in preparing injectable dosage forms is exempt from this requirement.]
Limit of iron—
Standard preparations—
Separately transfer 2.0,4.0,and 10.0mLof Standard Iron Solution,prepared as directed under Iron á241ñ,to 100-mLvolumetric flasks,each containing 1.37g of calcium chloride,previously tested and shown to contain less than 5ppm of iron,dilute with 2Nhydrochloric acid to volume,and mix.These solutions contain,respectively,0.2,0.4,and 1.0µg of iron per mL.
Test preparation—
Transfer 1.0g of Calcium Gluconate to a 100-mLquartz glass flask,add 20mLof 12Nnitric acid,and heat to boiling until fumes are evolved.Add 0.5mLof 30%hydrogen peroxide,and heat again until fumes are evolved.Repeat this process until the volume is reduced to about 5mL.Cool,add 1.0mLof perchloric acid,and heat to boiling.[Caution—Do not heat above 190or evaporate to dryness because of danger of explosion.
]Transfer this solution to a 25-mLvolumetric flask,dilute with 2Nhydrochloric acid to volume,and mix.
or evaporate to dryness because of danger of explosion.
]Transfer this solution to a 25-mLvolumetric flask,dilute with 2Nhydrochloric acid to volume,and mix.
Blank solution—
Using 0.34g of calcium chloride,previously tested and shown to contain less than 5ppm of iron,instead of Calcium Gluconate,prepare as directed under Test preparation.
Procedure—
Concomitantly determine the absorbances of the Standard preparationsand the Test preparationat the iron emission line of 248.3nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-Scattering á851ñ)equipped with an iron hollow-cathode lamp and an air–acetylene flame,using the Blank solutionas the blank and making deuterium background corrections.Plot the absorbances of the Standard preparationsversus concentration,in µg per mL,of iron,and draw the straight line best fitting the three plotted points.From the graph so obtained,determine the concentration,C,in µg per mL,of iron in the Test preparation.Calculate the concentration of iron,in ppm,in the specimen taken by the formula:
25C.
The limit is 5ppm.[NOTE—Calcium Gluconate labeled as not intended for use in the preparation of injectable dosage forms is exempt from this requirement.]
Reducing substances—
Transfer 1.0g to a 250-mLconical flask,dissolve in 20mLof hot water,cool,and add 25mLof alkaline cupric citrate TS.Cover the flask,boil gently for 5minutes,accurately timed,and cool rapidly to room temperature.Add 25mLof 0.6Nacetic acid,10.0mLof 0.1Niodine VS,and 10mLof 3Nhydrochloric acid,and titrate with 0.1Nsodium thiosulfate VS,adding 3mLof starch TSas the endpoint is approached.Perform a blank determination,omitting the specimen,and note the difference in volumes required.Each mLof the difference in volume of 0.1Nsodium thiosulfate consumed is equivalent to 2.7mg of reducing substances (as dextrose):the limit is 1.0%.
Organic volatile impurities,Method Iá467ñ:
meets the requirements.
Assay—
Dissolve about 800mg of Calcium Gluconate,accurately weighed,in 150mLof water containing 2mLof 3Nhydrochloric acid.While stirring,preferably with a magnetic stirrer,add about 30mLof 0.05Medetate disodium VSfrom a 50-mLburet.Add 15mLof 1Nsodium hydroxide and 300mg of hydroxy naphthol blue,and continue the titration to a blue endpoint.Each mLof 0.05Medetate disodium is equivalent to 21.52mg of C12H22CaO14.
Auxiliary Information—
Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(DSN)Dietary Supplements:Non-Botanicals
USP28–NF23Page 326
Pharmacopeial Forum:Volume No.27(6)Page 3258
Phone Number:1-301-816-8389