»Heparin Calcium is the calcium salt of sulfated glycosaminoglycans present as a mixture of heterogeneous molecules of mixed mucopolysaccharide nature varying in molecular weights.It is present in mammalian tissues and is usually obtained from the intestinal mucosa or other suitable tissues of domestic mammals used for food by humans.It is purified to retain a combination of activities against different fractions of the blood clotting sequence.It is composed of polymers of alternating derivatives of D-glucosamine (N-sulfated,O-sulfated,or N-acetylated)and uronic acid (L-iduronic acid or D-glucuronic acid)joined by glycosidic linkages.The component activities of the mixture are in ratios corresponding to those shown by the USP Heparin Sodium Reference Standard.Some of these components have the property of prolonging the clotting time of blood.This occurs through the formation of a complex of each component with the plasma proteins antithrombin IIIand heparin cofactor IIto potentiate the inactivation of thrombin.Other coagulation proteases in the clotting sequence,such as activated factor X(factor Xa),are also inhibited.The potency of Heparin Calcium,calculated on the dried basis,is not less than 140USP Heparin Units in each mg,and not less than 90.0percent and not more than 110.0percent of the potency stated on the label.Heparin Calcium is essentially free from sodium.
NOTEThe USP Heparin Unit is defined by the USP Heparin Sodium Reference Standard,independent of International Units.The respective units are not equivalent (see General Notices).Unit for Anti-factor Xaactivity is defined by the USP Heparin Sodium Reference Standard.
Packaging and storage Preserve in tight containers,and store at a temperature below 40,preferably at room temperature.
Labeling Label it to indicate the tissue and the animal species from which it is derived.
A: It responds to the flame test for Calcium á191ñ.
Bacterial endotoxins á85ñ It contains not more than 0.03Endotoxin Unit per USP Heparin Unit.
Add the following:Sterility á71ñ(where it is labeled as sterile) It meets the requirements.USP28
pHá791ñ: between 5.0and 7.5,in a solution (1in 100).
Loss on drying á731ñ Dry it in vacuum at 60for 3hours:it loses not more than 5.0%of its weight.
Residue on ignition á281ñ: between 28.0%and 41.0%.
Protein To 1mLof a solution (1in 100)add 5drops of trichloroacetic acid solution (1in 5):no precipitate or turbidity forms.
Heavy metals,Method IIá231ñ: 0.003%.
Anti-factor Xaactivity Proceed as directed in the test for Anti-factor Xaactivityunder Heparin Sodium,except to use Heparin Calcium instead of Heparin Sodium to prepare the Test solutions.The specified results are obtained.
Nitrogen content,Method Iá461ñ: between 1.3%and 2.5%,calculated on the dried basis,the procedure for Nitrates and Nitrites Absentbeing used.
Assay Proceed as directed in the Assayunder Heparin Sodium,except to use Heparin Calcium solution to prepare the Assay preparation.In the equation for Rin the Calculationsection,vUis the amount in mg of Heparin Calcium per mLof the Assay preparation.The potency of Heparin Calcium in USP Heparin Units per mg is P*=antilog bar(M).
Auxiliary Information Staff Liaison:Radhakrishna S Tirumalai,Scientist
Expert Committee:(BBP)Blood and Blood Products
USP28NF23Page 940Pharmacopeial Forum:Volume No.29(6)Page 1898