Dipotassium hydrogen phosphate is a highly water-soluble salt extensively used as a fertilizer, food additive, and buffer. Dipotassium hydrogen phosphate could be utilized as pharmaceutical excipients, such as pH adjusters and buffers. Pharmaceutical excipients or pharmaceutical auxiliaries refer to other chemical substances other than drug ingredients used in the pharmaceutical process. Pharmaceutical excipients generally refer to inactive ingredients in pharmaceutical preparations, which can improve the stability, solubility and processability of pharmaceutical preparations. Pharmaceutical excipients can also affect the absorption, distribution, metabolism, and elimination (ADME) processes of co-administered drugs.

Physicochemical Properties

Molecular Formula	HK2O4P
Molecular Weight	174.18
Exact Mass	173.888
CAS #	7758-11-4
Related CAS #	16068-46-5 (Parent)
PubChem CID	24450
Appearance	White crystals Colorless or white granules or powder
Density	2,44 g/cm3
Boiling Point	158ºC at 760 mmHg
Melting Point	340 °C
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	0
Heavy Atom Count	7
Complexity	46.5
Defined Atom Stereocenter Count	0
SMILES	[K+].[K+].P(=O)([O-])([O-])O[H]
InChi Key	ZPWVASYFFYYZEW-UHFFFAOYSA-L
InChi Code	InChI=1S/2K.H3O4P/c;;1-5(2,3)4/h;;(H3,1,2,3,4)/q2*+1;/p-2
Chemical Name	dipotassium;hydrogen phosphate
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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 Potassium salts are well absorbed from gastro intestinal tract. Net phosphorus absorption may occur in the small intestine in some species but is primarily a function of the colon in horses. Potassium is excreted primarily by kidney. Distribution is largely intracellular, but it is the intravascular concentration that is primarily responsible for toxicity. Phosphates are rapidly cleared by dialysis. POTASSIUM SALTS ARE WELL ABSORBED FROM THE GASTROINTESTINAL TRACT. ... POTASSIUM IS EXCRETED PRIMARILY BY THE KIDNEY. /POTASSIUM SALTS/ Net phosphorus absorption may occur in the small intestine in some species but is primarily a function of the colon in horses. /SRP: Phosphates/ /Ortho/ phosphate is absorbed from, and to a limited extent secreted into, the gastrointestinal tract. Transport of phosphate from the gut lumen is an active, energy-dependent process that is modified by several factors. ... Vitamin D stimulates phosphate absorption, an effect reported to precede its action on calcium ion transport. In adults, about two thirds of the ingested phosphate is absorbed, and that which is absorbed is almost entirely excreted into the urine. In growing children, phosphate balance is positive. Concentrations of phosphate in plasma are higher in children than in adults. This "hyperphosphatemia" decreases the affinity of hemoglobin for oxygen and is hypothesized to explain the physiological "anemia" of childhood. /Phosphates/ Metabolism / Metabolites Phosphate is a major intracellular anion which participates in providing energy for metabolism of substances and contributes to important metabolic and enzymatic reactions in almost all organs and tissues. Biological Half-Life In healthy children with phosphate overdose, half-life was 4.8 to 10.6 hours, and was prolonged to 17 hours in a child with renal insufficiency.
Toxicity/Toxicokinetics	Protein Binding Phosphate is minimally protein bound, and highly concentrated in cells (intracellular concentrations are 100-fold higher than serum concentrations). Concentrations of phosphate in plasma are higher in children than in adults.
References	[1]. Effect of dipotassium hydrogen phosphate on thermodynamic properties of glycine and l-alanine in aqueous solutions at different temperatures. The Journal of Chemical Thermodynamics, 2012, 53: 86-92. [2]. Pharmaceutical excipients - quality, regulatory and biopharmaceutical considerations. Eur J Pharm Sci. 2016 May 25;87:88-99.
Additional Infomation	Dipotassium hydrogen phosphate is a potassium salt that is the dipotassium salt of phosphoric acid. It has a role as a buffer. It is a potassium salt and an inorganic phosphate. Dipotassium phosphate (K2HPO4) is a highly water-soluble salt often used as a fertilizer and food additive as a source of phosphorus and potassium as well as a buffering agent. Potassium Phosphate, Dibasic is the dipotassium form of phosphoric acid, that can be used as an electrolyte replenisher and with radio-protective activity. Upon oral administration, potassium phosphate is able to block the uptake of the radioactive isotope phosphorus P 32 (P-32). Drug Indication Dipotassium phosphate is used in imitation dairy creamers, dry powder beverages, mineral supplements, and starter cultures as an additive. It is used in non-dairy creamers to prevent coagulation. Dipotassium phosphate is also used to make buffer solutions and it is used in the production of trypticase soy agar which is used to make agar plates for culturing bacteria. Mechanism of Action Once phosphate gains access to the body fluids and tissues, it exerts little pharmacological effect. If the ion is introduced into the intestine, the absorbed phosphate is rapidly excreted. If large amounts are given by this route, much of it may escape absorption. Because this property leads to a cathartic action, phosphate salts are employed as mild laxatives. Once phosphate gains access to the body fluids and tissues, it exerts little pharmacological effect. If the ion is introduced into the intestine, the absorbed phosphate is rapidly excreted. If large amounts are given by this route, much of it may escape absorption. Because this property leads to a cathartic action, phosphate salts are employed as mild laxatives. Inorganic phosphate poisoning following ingestion of laxatives that contain phosphate salts has been reported in adults and children. Ingestion of large amounts of sodium dihydrogen phosphate lowers urinary pH. If excessive phosphate salts are introduced intravenously or orally, they may prove toxic by reducing the concentration of Ca 2+ in the circulation and from the precipitation of calcium phosphate in soft tissues. /Phosphates/ Therapeutic Uses CATHARTIC Factors affecting calcium-phosphate solubility in parenteral nutrition solutions used in neonates were studied. Six neonatal parenteral nutrition solutions were prepared using either Aminosyn or FreAmine II and various amino acid and dextrose concentrations. Phosphorus (as mono- and dibasic potassium phosphate) and calcium (as 10% calcium gluconate) were added in concentrations of calcium 2.5-100 meq/l and phosphorus 2.5-100 mmol/l. Duplicate samples were prepared and analyzed either after they were heated in a water bath (37 °C) for 20 min or after 18 hr at 25 °C followed by 30 min in a water bath (37 °C). Precipitation was detected visually and spectrophotometrically, and pH was measured. Lipid emulsion was added to 2 FreAmine II solutions in a ratio of 7.5:1 (parenteral nutrition solution:lipid) and the resulting pH was measured. Time and temperature affected calcium-phosphate solubility in all solutions tested. Precipitation curves of amount of calcium versus amount of phosphate added were prepared for each solution. Amino acid and dextrose concentrations affected the pH of the solutions, and when a lipid emulsion was added, the pH rose more in the 1% than in the 2% FreAmine II solution. In selected solutions, as much as 120 mg/kg/day calcium and 55 mg/kg/day phosphate can be administered, approximating daily third trimester accumulation of these minerals. Use of the precipitation curves in this paper, with attention to their limitations, should aid in the safe delivery of calcium and phosphorus IV to neonates. SALINE BULK CATHARTIC Drug Warnings Oral administration is safer, but careful monitoring of serum electrolyte levels and renal function is necessary. Nausea, vomiting, and diarrhea may occur and may be dose dependent. Concomitant use of antacids containing aluminum and/or magnesium should be avoided, because they may bind phosphate and prevent it absorption (calcium antacids also may bind phosphate, and it is assumed that these agents are not given to hypercalcemic patients). Phosphate should not be given to patients with impaired renal function or hyperphosphatemia. They should not be given to patients with alkaline urine due to urinary tract infections because increased calcium and phosphate concentrations in the alkaline urine increase the risk of calcium phosphate stones. Intravenous administration of phosphates is dangerous. Hypocalcemia, hypotension and shock, myocardial infarction, tetany, and acute renal failure have occurred, and deaths have been reported. Deposition of calcium phosphate in the kidney, heart, lung, and blood vessels also may be fatal. For these reasons, intravenous therapy is not justified in the treatment of hypercalcemia. Phosphates should not be administered to patients with impaired renal function or hyperphosphatemia. They also should not be given to patients with alkaline urine due to urinary tract infections because increased calcium and phosphate concentrations in the alkaline urine increase the risk of calcium phosphate stones. Phosphate should be given as the potassium rather than the sodium salt because the latter causes volume expansion and inhibits phosphate reabsorption, thus negating the therapeutic effect. /Phosphate salt/ The most common adverse effect of phosphate salts is diarrhea. Patients with kidney stones may pass old stones when phosphate therapy is started and should be warned of this possibility. Phosphates are contraindicated in patients with infected stones and in those with renal function less than 30% of normal. /Orthophosphates/ Pharmacodynamics Phosphate is a major intracellular anion which participates in providing energy for metabolism of substances and contributes to important metabolic and enzymatic reactions in almost all organs and tissues. Phosphate exerts a modifying influence on calcium concentrations, a buffering effect on acid-base equilibrium, and has a major role in the renal excretion of hydrogen ions.

Solubility Data

Solubility (In Vitro)

H2O: 50 mg/mL (287.06 mM)

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	5.7412 mL	28.7059 mL	57.4119 mL
	5 mM	1.1482 mL	5.7412 mL	11.4824 mL
	10 mM	0.5741 mL	2.8706 mL	5.7412 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.