Calcium disodium edetate hydrate is a biochemical compound that could be utilized as a biomaterial or organic/chemical reagent for biomedical research.

Physicochemical Properties

Molecular Formula	C10H14CAN2NA2O9
Molecular Weight	392.2837
Exact Mass	374.001
CAS #	23411-34-9
PubChem CID	6093170
Appearance	Powder White powder or flakes
Boiling Point	614.2ºC at 760 mmHg
Melting Point	>300
Flash Point	325.2ºC
Vapour Pressure	1.15E-16mmHg at 25°C
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	23
Complexity	293
Defined Atom Stereocenter Count	0
SMILES	[Ca+2].[Na+].[Na+].[O-]C(C([H])([H])N(C([H])([H])C(=O)[O-])C([H])([H])C([H])([H])N(C([H])([H])C(=O)[O-])C([H])([H])C(=O)[O-])=O.O([H])[H]
InChi Key	SHWNNYZBHZIQQV-UHFFFAOYSA-J
InChi Code	InChI=1S/C10H16N2O8.Ca.2Na/c13-7(14)3-11(4-8(15)16)1-2-12(5-9(17)18)6-10(19)20;;;/h1-6H2,(H,13,14)(H,15,16)(H,17,18)(H,19,20);;;/q;+2;2*+1/p-4
Chemical Name	calcium;disodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ADME/Pharmacokinetics	Absorption, Distribution and Excretion Calcium edetate disodium's Cmax and AUC are dependant on renal function. 5% of an oral dose is absorbed from the gastrointestinal tract. Edetate calcium disodium is 95% eliminated in the urine within 24 hours. An oral dose in rats was 88.32% recovered in the feces and 10.30% recovered in the urine. The volume of distribution of edetate calcium disodium is 0.19±0.10L/kg. The mean clearance of edetate in 1 month olds is 54.6mL/min/1.73m2. 2-17 year olds have a mean clearance of 113.9±24.4mL/min/1.73m2. Edetate calcium disodium is poorly absorbed from the gastrointestinal tract. Edetate calcium disodium is well absorbed following IM or subcutaneous administration. When edetate calcium disodium is administered IV in the treatment of lead poisoning, urinary excretion of chelated lead begins within about 1 hour and peak excretion of chelated lead occurs within 24-48 hours. Colic caused by lead poisoning may disappear within 2 hours, muscular weakness and tremors disappear after 4-5 days, and coproporphyrinuria and stippled erythrocytes usually decrease within 4-9 days after therapy is initiated. Edetate calcium disodium is distributed mainly into extracellular fluid. The drug does not penetrate erythrocytes... Following parenteral administration, it is rapidly excreted by glomerular filtration in urine, either unchanged or as metal chelates. Following IV administration, 50% of a dose appears in urine within 1 hour and 95% within 24 hours. ... Changes in urine flow and/or pH do not affect the excretion rate of edetate calcium disodium, but impaired renal function with reduced glomerular filtration delays excretion of the drug and thus may increase its nephrotoxicity. For more Absorption, Distribution and Excretion (Complete) data for DISODIUM CALCIUM EDTA (10 total), please visit the HSDB record page. Metabolism / Metabolites Edetate calcium disodium is almost completely unmetabolized _in vivo_. Edetate calcium disodium is not metabolized. Biological Half-Life The half life of edetate calcium disodium is 20-60 minutes. The plasma half-life of the drug has been reported to be 20-60 minutes following IV administration and 1.5 hours following IM administration.
Toxicity/Toxicokinetics	Interactions Zinc supplements (concurrent use may decrease the effectiveness of edetate calcium disodium and zinc supplements due to chelation; zinc supplement therapy should be withheld until edetate calcium disodium therapy is completed) Edetate calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc. Concomitant administration of CaNa2EDTA and dimercaprol (BAL) increases the rate of lead mobilization from tissue depots and probably reduces the incidence of central nervous system toxicity when compared with the single use of CaNa2EDTA. Steroids enhance the renal toxicity of edetate calcium disodium in animals. Non-Human Toxicity Values LD50 Rat oral 10 g/kg LD50 Rat ip 3.85 g/kg LD50 Rat iv 3 g/kg LD50 Mouse ip 4.5 g/kg For more Non-Human Toxicity Values (Complete) data for DISODIUM CALCIUM EDTA (6 total), please visit the HSDB record page.
Additional Infomation	EDTA monocalcium diisodium salt is an organic calcium salt of EDTA diisodium. It is a chelating agent that is used for the treatment of lead poisoning. It has a role as a geroprotector, a chelator and an antidote. It contains an EDTA disodium salt (anhydrous). Edetate calcium disodium is a metal ion chelator used to reduce blood concentrations and depot stores of lead from the body. It is on the World Health Organization Model List of Essential Medicines. Edetate calcium disodium was granted FDA approval on 16 July 1953. Edetate Calcium Disodium is contracted name for a salt of ethylenediaminetetraacetate, an agent used as a chelator of lead and some other heavy metals. C10H12CaN2Na2O8. A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive. Drug Indication Edetate calcium disodium is indicated to reduce blood levels and depot stores of lead in acute and chronic lead poisoning. Mechanism of Action Edetate calcium disodium distributes into tissues, such as the kidney and bone, where it chelates lead ions. The lead ions are then eliminated in the normal urinary excretion of edetate. Lead in certain tissues such as the liver and bone, redistribute to other tissues after edetate calcium disodium treatment, but lead levels do not decrease to levels seen in unexposed patients. The calcium in edetate calcium disodium can be displaced by divalent and trivalent metals, particularly lead, to form stable soluble complexes that can then be excreted in urine. Unlike edetate disodium (no longer commercially available in the US), edetate calcium disodium is saturated with calcium and therefore can be administered IV in relatively large quantities without causing any substantial changes in serum or total body calcium concentrations. Although 1 g of edetate calcium disodium theoretically sequesters 620 mg of lead, an average of only 3-5 mg of lead is excreted in urine following parenteral administration of 1 g of the drug to patients with symptoms of acute lead poisoning or with high concentrations of lead in soft tissues. Parenteral administration of edetate calcium disodium chelates and greatly increases the urinary excretion of zinc and, to a much lesser extent, cadmium, manganese, iron, and copper. Excretion of uranium, plutonium, yttrium, and some other heavier radioactive isotopes can be increased to a limited extent by edetate calcium disodium chelation. Although mercury readily displaces calcium from edetate calcium disodium in vitro, patients with mercury poisoning do not respond to the drug. The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron mobilized are not significant. Copper is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased. The primary source of lead chelated by calcium disodium edetate is from bone; subsequently, soft-tissue lead is redistributed to bone when chelation is stopped. There is also some reduction in kidney lead levels following chelation therapy. For more Mechanism of Action (Complete) data for DISODIUM CALCIUM EDTA (6 total), please visit the HSDB record page. Therapeutic Uses Edetate calcium disodium is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults. Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead. /Included in US product label/ The US Food and Drug Administration (FDA) states that the safety and effectiveness of edetate calcium disodium for use in removing heavy metals (eg, mercury) and toxins from the body, management of coronary artery disease, or other uses not described in the manufacturer's labeling have not been established. VET: Chelating agent in lead poisoning. /SRP: Former use/ EDTA lead-mobilization test has proved to be a sensitive indicator of excessive body stores of lead. This test was used to evaluate cumulative past lead absorption in 48 men diagnosed as having essential hypertension, a disease considered a possible complication of lead poisoning. For more Therapeutic Uses (Complete) data for DISODIUM CALCIUM EDTA (8 total), please visit the HSDB record page. Drug Warnings /BOXED WARNING/ WARNINGS: Calcium Disodium Versenate is capable of producing toxic effects which can be fatal. Lead encephalopathy is relatively rare in adults, but occurs more often in pediatric patients in whom it may be incipient and thus overlooked. The mortality rate in pediatric patients has been high. Patients with lead encephalopathy and cerebral edema may experience a lethal increase in intracranial pressure following, intravenous infusion; the intramuscular route is preferred for these patients. In cases where the intravenous route is necessary, avoid rapid infusion. The dosage schedule should be followed and at no time should the recommended daily dose be exceeded. Fatal medication errors have occurred that involve confusion between edetate calcium disodium (calcium EDTA) and edetate disodium (no longer commercially available in the US). Children and adults have mistakenly received edetate disodium instead of edetate calcium disodium; at least 5 deaths have occurred as a result of inadvertent administration of edetate disodium. Although both edetate calcium disodium and edetate disodium are heavy metal antagonists, the 2 drugs were originally approved by the US Food and Drug Administration (FDA) for different uses and have different effects; edetate disodium was formerly FDA approved for use in selected patients for the emergency treatment of hypercalcemia or for the control of ventricular arrhythmias associated with cardiac glycoside toxicity. Use of edetate disodium may result in a substantial, and sometimes fatal, decrease in serum calcium concentrations. In June 2008, FDA withdrew its prior approval for edetate disodium because of safety concerns following a review of the risk-benefit profile of the drug. FDA stated that it was not considering additional action regarding edetate calcium disodium at that time; most of the fatalities following administration of an EDTA drug have involved medication errors in which edetate disodium was administered instead of edetate calcium disodium. FDA has not received reports of any fatalities resulting from the administration of edetate calcium disodium that involve a medication error. The manufacturer states that the drug is contraindicated in patients with anuria and in those with active renal disease. Edetate calcium disodium also is contraindicated in patients with hepatitis. The principal and most serious toxic effect of edetate calcium disodium is renal tubular necrosis, which tends to occur when the daily dose is excessive and may result in fatal nephrosis. Edetate calcium disodium may produce the same signs of renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Rarely, changes in distal renal tubules and glomeruli, glycosuria, presence of large renal epithelial cells in urinary sediment, increased urinary frequency, and urgency may occur. Hydropic degeneration of proximal renal tubular cells also may occur; however, recovery usually occurs following discontinuance of therapy. For more Drug Warnings (Complete) data for DISODIUM CALCIUM EDTA (24 total), please visit the HSDB record page. Pharmacodynamics Edetate calcium disodium is a polyvalent ion chelator used to remove lead from the body after lead poisoning. It has a wide therapeutic index, as overdoses must be well in excess of the therapeutic dose to show symptoms. It has a long duration of action, as doses are given at least a day apart. Patients should be counselled regarding the risk of increased intracranial pressure with intravenous infusions.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5492 mL	12.7460 mL	25.4920 mL
	5 mM	0.5098 mL	2.5492 mL	5.0984 mL
	10 mM	0.2549 mL	1.2746 mL	2.5492 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.