Oral Rehydration Salts
»Oral Rehydration Salts is a dry mixture of Sodium Chloride,Potassium Chloride,Sodium Bicarbonate,and Dextrose (anhydrous).Alternatively,it may contain Sodium Citrate (anhydrous or dihydrate)instead of Sodium Bicarbonate.It may contain Dextrose (monohydrate)instead of Dextrose (anhydrous),provided that the Sodium Bicarbonate or Sodium Citrate is packaged in a separate,accompanying container.It contains the equivalent of not less than 90.0percent and not more than 110.0percent of the amounts of sodium (Na+),potassium (K+),chloride (Cl-),and bicarbonate (HCO3-)or citrate (C6H5O7-3),calculated from the labeled amounts of Sodium Chloride,Potassium Chloride,and Sodium Bicarbonate [or Sodium Citrate (anhydrous or dihydrate)].It contains not less than 90.0percent and not more than 110.0percent of the labeled amounts of anhydrous dextrose (C6H12O6),or dextrose monohydrate (C6H12O6·H2O).It may contain suitable flavors.
Packaging and storage— Preserve in tight containers,and avoid exposure to temperatures in excess of 30.The Sodium Bicarbonate or Sodium Citrate component may be omitted from the mixture and packaged in a separate,accompanying container.
Labeling— The label indicates prominently whether Sodium Bicarbonate or Sodium Citrate is a component by the placement of the word “Bicarbonate”or “Citrate,”as appropriate,in juxtaposition to the official title.The label states the name and quantity,in g,of each component in each unit-dose container,or in a stated quantity,in g,of Salts in a multiple-unit container.The label states the net weight in each container and provides directions for constitution.Where packaged in individual unit-dose pouches,the label instructs the user not to open until the time of use.The label states also that any solution that remains unused 24hours after constitution is to be discarded.
Identification—
A: It responds to the flame tests for Sodium á191ñand for Potassium á191ñ.
B: It responds to the tests for Chloride á191ñ.
C: Where it contains Sodium Bicarbonate,it dissolves with effervescence,and the collected gas so obtained responds to the test for Bicarbonate á191ñ.
D: Where it contains Sodium Citrate,it responds to the tests for Citrate á191ñ,3to 5drops of the solution constituted as directed in the labeling and 20mLof the mixture of pyridine and acetic anhydride being used.
E: Where it contains Dextrose,add a few drops of the solution constituted as directed in the labeling to 5mLof hot alkaline cupric tartrate TS:a copious red precipitate of cuprous oxide is formed (presence of dextrose).
F: When heated it melts,swells,and burns,yielding the odor of burnt sugar.
Loss on drying á731ñ— Dry it at 50to constant weight:it loses not more than 1.0%of its weight.
Minimum fill á755ñ— Proceed as directed,except to change the requirements following “The average net weight of the contents of the 10containers is not less than the labeled amount,and the net weight of the contents of any single container is not less than”to read “95%and not more than 105%of the labeled amount.If the contents of not more than 1container are less than 95%but not less than 90%of the labeled amount or more than 105%but not more than 110%of the labeled amount,determine the net weight of the contents of 20additional containers.The average net weight of the contents of 30containers is not less than the labeled amount,and the net weight of the contents of not more than 1of the 30containers is less than 95%but not less than 90%of the labeled amount or more than 105%but not more than 110%of the labeled amount.”
NOTE—In performing the Assay for sodium and potassium,the Assay for chloride,the Assay for bicarbonate,and the Assay for citrate,calculate from the labeled amounts of sodium chloride,potassium chloride,and sodium bicarbonate or sodium citrate the total equivalent amounts of sodium (Na+),potassium (K+),chloride (Cl-),and bicarbonate (HCO3-),[or citrate (C6H5O7-3)]contained therein.(See accompanying table.)
mg equivalent of each g of component
Component Na+ K+ Cl- HCO3- C6H5O7-3
Sodium Chloride 393.4 606.6
Potassium Chloride 524.4 475.6
Sodium Bicarbonate 273.6 726.4
Anhydrous Sodium Citrate 267.2 732.8
Sodium Citrate Dihydrate 234.5 643.0
pHá791ñ: between 7.0and 8.8,in the solution constituted as directed in the labeling.
Assay for dextrose— Transfer the contents of 1or more unit-dose containers of Oral Rehydration Salts,or an accurately weighed portion of the contents of 1multiple-unit container,equivalent to about 20g of dextrose,to a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 50.0mLof this stock solution to a 100-mLvolumetric flask.Add 0.2mLof 6Nammonium hydroxide,dilute with water to volume,and mix.[NOTE—Reserve the remaining stock solution for the Assay for sodium and potassium,the Assay for chloride,the Assay for bicarbonate,and the Assay for citrate.]Determine the angular rotation in a suitable polarimeter tube at 25(see Optical Rotation á781ñ).Calculate the quantity,in g,of anhydrous dextrose (C6H12O6)in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container,by the formula:
(200/52.7)(a/l),
in which 52.7is the specific rotation of anhydrous dextrose,ais the corrected observed rotation,in degrees,and lis the length,in dm,of the polarimeter tube.Where the Oral Rehydration Salts is labeled to contain Dextrose Monohydrate,calculate the quantity of dextrose monohydrate (C6H12O6·H2O)by the same formula,substituting the figure 47.9,the specific rotation of dextrose monohydrate,in place of 52.7.
Assay for sodium and potassium—
Sodium stock solution— Transfer 14.61g of sodium chloride,previously dried at 105for 2hours and accurately weighed,to a 250-mLvolumetric flask,add water to volume,and mix.
Potassium stock solution— Transfer 18.64g of potassium chloride,previously dried at 105for 2hours and accurately weighed,to a 250-mLvolumetric flask,add water to volume,and mix.
Lithium diluent solution— Transfer 1.04g of lithium nitrate to a 1000-mLvolumetric flask,add a suitable nonionic surfactant,then add water to volume,and mix.
Standard preparation— Transfer 5.0mLof Sodium stock solution and 5.0mLof Potassium stock solutionto a 500-mLvolumetric flask,dilute with water to volume,and mix.Transfer 5.0mLof the resulting solution to a 100-mLvolumetric flask,dilute with Lithium diluent solutionto volume,and mix.Each mLof this solution contains 0.01150mg of sodium (Na+)and 0.01955mg of potassium (K+).
Assay preparation 1— Dilute an accurately measured volume of the stock solution remaining from the Assay for dextrosequantitatively,and stepwise if necessary,with water to obtain a solution containing about 0.23mg of sodium (Na+)per mL.Transfer 5.0mLof the resulting solution to a 100-mLvolumetric flask,dilute with Lithium diluent solutionto volume,and mix.
Assay preparation 2— Dilute an accurately measured volume of the stock solution remaining from the Assay for dextrosequantitatively,and stepwise if necessary,with water to obtain a solution containing about 0.39mg of potassium per mL.Transfer 5.0mLof the resulting solution to a 100-mLvolumetric flask,dilute with Lithium diluent solutionto volume,and mix.
Procedure— Using a suitable flame photometer,adjusted to read zero with Lithium diluent solution,concomitantly determine the sodium flame emission readings for the Standard preparationand Assay preparation 1at the wavelength of maximum emission at about 589nm.Calculate the quantity,in mg,of Na+in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container by the formula:
0.23(LNa/DNa)(RU,Na/RS,Na),
in which LNais the quantity,in mg,of sodium (Na+)in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container,calculated from the labeled quantities of sodium chloride and sodium bicarbonate (or sodium citrate),DNais the concentration,in mg per mL,of sodium in Assay preparation 1,based on the volume taken of the stock solution remaining from the Assay for dextroseand the extent of dilution,and RU,Naand RS,Naare the sodium emission readings obtained from Assay preparation 1and the Standard preparation,respectively.Similarly determine the potassium flame emission readings from the Standard preparationand Assay preparation 2at the wavelength of maximum emission at about 766nm.Calculate the quantity,in mg,of K+in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container by the formula:
0.391(LK/DK)(RU,K/RS,K),
in which LKis the quantity,in mg,of potassium in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container,calculated from the labeled quantity of potassium chloride,DKis the concentration,in mg per mL,of potassium in Assay preparation 2,based on the volume taken of the stock solution remaining from the Assay for dextroseand the extent of dilution,and RU,Kand RS,Kare the potassium emission readings obtained from Assay preparation 2and the Standard preparation,respectively.
Assay for chloride— Transfer an accurately measured volume of the stock solution remaining from the Assay for dextrose,equivalent to about 55mg of chloride (Cl-),to a suitable container,and titrate with 0.1Nsilver nitrate VSuntil the silver chloride flocculates and the mixture acquires a faint pink color using potassium chromate TSas the indicator.Calculate the quantity,in mg,of Cl-in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container by the formula:
354.5T/v,
in which Tis the volume,in mL,of 0.1Nsilver nitrate consumed,and vis the volume,in mL,of stock solution taken.
Assay for bicarbonate (if present)— Transfer an accurately measured volume of the stock solution remaining from the Assay for dextrose,equivalent to about 100mg of bicarbonate (HCO3-),to a suitable beaker,add 25mLof water and 3drops of methyl orange TS,and titrate with 0.1Nhydrochloric acid VS.Calculate the quantity,in mg,of HCO3-in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container,by the formula:
610.2T/v,
in which Tis the volume,in mL,of 0.1Nhydrochloric acid consumed,and vis the volume,in mL,of the stock solution taken.
Assay for citrate (if present)—
Mobile phase— Dissolve 20g of ammonium sulfate in a mixture of water and acetonitrile (980:20).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Standard preparation— Dissolve an accurately weighed quantity of sodium citrate,previously dried at 180for 18hours,in water to obtain a solution having a known concentration of about 2.5mg of anhydrous sodium citrate per mL.
Assay preparation— Transfer an accurately measured volume of the stock solution remaining from the Assay for dextrose,equivalent to about 180mg of citrate (C6H5O7-3),to a 100-mLvolumetric flask,dilute with water to volume,and mix.
Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 220-nm detector and a 4.8-mm ×20-cm column that contains packing L8.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak response as directed for Procedure:the retention time for the citrate peak is about 3minutes,the column efficiency is not less than 1000theoretical plates,the tailing factor is not more than 2.0,and the relative standard deviation for replicate injections is not more than 2.0%.[NOTE—The column may be equilibrated before use by making a series of injections of the Standard preparation over a period of several hours.If the tailing factor is greater than 2,the equilibration may be facilitated by adding 1g of sodium citrate to each 1000mLof the Mobile phase and pumping this solution through the column at about 0.5mLper minute for several hours.The column must then be washed with Mobile phase for a few minutes before use.]
Procedure— Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of C6H5O7-3in the unit-dose container or containers taken or in the portion of powder taken from the multiple-unit container by the following formula:
(189.12/258.07)(10,000C/v)(rU/rS),
in which 189.12and 258.07are the molecular weights of citrate (C6H5O7-3)and anhydrous sodium citrate,respectively,Cis the concentration,in mg per mL,of anhydrous sodium citrate in the Standard preparation,vis the volume,in mL,of the stock solution taken to prepare the Standard preparation,and rUand rSare the citrate peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1708
Pharmacopeial Forum:Volume No.30(5)Page 1646
Phone Number:1-301-816-8379