Ringer's Injection
»Ringer's Injection is a sterile solution of Sodium Chloride,Potassium Chloride,and Calcium Chloride in Water for Injection.It contains,in each 100mL,not less than 323.0mg and not more than 354.0mg of sodium (Na,equivalent to not less than 820.0mg and not more than 900.0mg of NaCl);not less than 14.9mg and not more than 16.5mg of potassium (K,equivalent to not less than 28.5mg and not more than 31.5mg of KCl);not less than 8.20mg and not more than 9.80mg of calcium (Ca,equivalent to not less than 30.0mg and not more than 36.0mg of CaCl2·2H2O);and not less than 523.0mg and not more than 580.0mg of chloride (Cl,as NaCl,KCl,and CaCl2·2H2O).Ringer's Injection contains no antimicrobial agents.
NOTE—The calcium,chloride,potassium,and sodium ion contents of Ringer's Injection are approximately 4.5,156,4,and 147.5milliequivalents per liter,respectively.
Sodium Chloride 8.6g
Potassium Chloride 0.3g
Calcium Chloride 0.33g
Water for Injection,a sufficient
quantity to make		 1000mL
Dissolve the three salts in the Water for Injection,filter until clear,place in suitable containers,and sterilize.
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 total osmolar concentration in mOsmol per liter.Where the contents are less than 100mL,the label alternatively may state the total osmolar concentration in mOsmol per mL.
Identification— It responds to the flame tests for Sodium á191ñand Potassium á191ñ,to the ammonium oxalate test for Calcium á191ñ,and to the tests for Chloride á191ñ.
Bacterial endotoxins á85ñ— It contains not more than 0.5USP Endotoxin Unit per mL.
pHá791ñ: between 5.0and 7.5.
Heavy metals á231ñ— Evaporate 67mLto a volume of about 20mL,add 2mLof 1Nacetic acid,and dilute with water to 25mL:the limit is 0.3ppm.
Other requirements— It meets the requirements under Injections á1ñ.
Assay for calcium— [NOTE—Concentrations of the Standard preparationsand the Assay preparationmay be modified to fit the linear or working range of the atomic absorption spectrophotometer.]
Lanthanum chloride solution— Transfer 17.69g of lanthanum chloride to a 200-mLvolumetric flask,add 100mLof water,and carefully add 50mLof hydrochloric acid.Mix,and allow to cool.Dilute with water to volume,and mix.
Blank solution— Transfer 5.0mLof Lanthanum chloride solutionto a 100-mLvolumetric flask,dilute with water to volume,and mix.
Calcium stock solution— Transfer 499.5mg of primary standard calcium carbonate to a 200-mLvolumetric flask,and add 10mLof water.Carefully add 5mLof diluted hydrochloric acid,and swirl to dissolve the calcium carbonate.Dilute with water to volume,and mix.This solution contains 1000µg of calcium (Ca)per mL.
Standard preparations— To three separate 100-mLvolumetric flasks,each containing 5.0mLof Lanthanum chloride solution,add 1.0,1.5,and 2.0mL,respectively,of Calcium stock solution.Dilute the contents of each flask with water to volume,and mix.These three solutions contain,10.0,15.0,and 20.0µg,respectively,of calcium (Ca)per mL.
Assay preparation— Transfer 20.0mLof Injection,equivalent to about 1.8mg of calcium (Ca),to a 100-mLvolumetric flask containing 5.0mLof Lathanum chloride solution.Dilute the contents of the flask with water to volume,and mix.
Procedure— Concomitantly determine the absorbances of the Standard preparationsand the Assay preparationat the calcium emission line at 422.7nm,with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering á851ñ)equipped with a calcium hollow-cathode lamp and an air–acetylene flame,using the Blank solutionas the blank.Plot the absorbances of the Standard preparationsversus concentration,in µg per mL,of calcium,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 calcium in the Assay preparation.Calculate the quantity,in mg,of calcium in each 100mLof the Injection taken by the formula:
0.5(C).
Assay for potassium—
Standard stock solution— Dissolve 190.7mg of potassium chloride,previously dried at 105for 2hours,in 50mLof water,transfer to a 1000-mLvolumetric flask,dilute with water to volume,and mix.Each mLof this solution contains 100µg of potassium.
Standard preparations— Dissolve 1.093g of sodium chloride in 100.0mLof water,and transfer 10mLof this solution to each of five 100-mLvolumetric flasks containing 10.0mLof a solution of a suitable nonionic wetting agent (1in 500).Dilute the contents of one of the flasks with water to volume to provide a blank.To the remaining flasks add,respectively,5.0,10.0,15.0,and 20.0mLof Standard stock solution,dilute with water to volume,and mix.
Assay preparation— Pipet 10mLof Injection into a 100-mLvolumetric flask,add 10.0mLof a solution of a suitable wetting agent (1in 500),dilute with water to volume,and mix.
Standard graph— Set a suitable flame photometer for maximum transmittance at a wavelength of about 766nm.Adjust the instrument to zero transmittance with the blank.Adjust the instrument to 100%transmittance with the most concentrated of the Standard preparations.Read the percentage transmittance of the other Standard preparations,and plot transmittances versus concentration of potassium.
Procedure— Adjust the instrument as directed under Standard graph,read the percentage transmittance of the Assay preparation,and calculate the potassium content,in mg per 100mL,of Injection.
Assay for sodium—
Standard stock solution— Dissolve 254.2mg of sodium chloride,previously dried at 105for 2hours,in 50mLof water,transfer to a 1000-mLvolumetric flask,dilute with water to volume,and mix.Each mLof this solution contains 100µg of sodium.
Standard preparations— Transfer to each of five 100-mLvolumetric flasks 10mLof a solution of a suitable nonionic wetting agent (1in 500).Dilute the contents of one of the flasks with water to volume to provide a blank.To the remaining flasks add,respectively,5.0,10.0,15.0,and 20.0mLof Standard stock solution,dilute with water to volume,and mix.
Assay preparation— Pipet 5mLof Injection into a 1000-mLvolumetric flask containing 100mLof a solution of a suitable wetting agent (1in 500),dilute with water to volume,and mix.
Procedure— Proceed as directed for Standard graphand for Procedurein the Assay for potassium,setting the flame photometer for maximum transmittance at a wavelength of about 589nm,instead of about 766nm.Calculate the sodium content,in mg per 100mL,of Injection.
Assay for chloride— Pipet 10mLof Injection into a conical flask,and add 10mLof glacial acetic acid,75mLof methanol,and 3drops of eosin Y TS.Titrate,with shaking,with 0.1Nsilver nitrate VSto a pink endpoint.Each mLof 0.1Nsilver nitrate is equivalent to 3.545mg of Cl.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1735
Pharmacopeial Forum:Volume No.27(4)Page 2777
Phone Number:1-301-816-8379