INDIGOTINE

Indigotine is used inks, dyes, sensors, batteries, cosmetics, detergents.
Indigotine is also used as a food colourant, a histological dye and a two-colour pH indicator.
Indigotine is used mucosal staining in endoscopy/surgery.

CAS Number: 860‑22‑0 
EC Number: 212‑728‑8 
Molecular Formula: C₁₆H₈N₂Na₂O₈S₂ 
Molar Mass: ~466.36 g/mol 

SYNONYMS:
Indigotine, Indigo Carmine, Indigotindisulfonate sodium, 5,5′‑indigodisulfonic acid sodium salt, Brilliant Indigo, FD&C Blue 2, CI Food Blue 1, Acid Blue 74, CI 73015, Sicovit Indigotin 85, C.I. Pigment Blue 63, CI 75781, Natural Blue 2, Indigo Carmine, CI Blue No. 1 Food Color, Disodium [2(2′)E]-3,3′-dioxo-1,1′,3,3′-tetrahydro[2,2′-biindolylidene]-5,5′-disulfonate, Indigotine, 5,5′-indigodisulfonic acid sodium salt, Brilliant Indigo, 4 G, C.I. Acid Blue 74, C.I. 73015, CI Food Blue 1, FD&C Blue 2, Sicovit Indigotin 85, E132, Indigotindisulfonate sodium, Indigo carmine, Acid Blue 74, Indigo Carmine, Indigotine, E 132, disodium 3,3‐dioxo‐2,2‐bi‐indolylidene‐5,5‐disulfonate, aniline, food additive, EINECS 212‐728‐8, FD&C Blue No. 2, Indigotindisulfonate sodium, Acid Blue 74, Indigocarmine, Indigo‑5,5′‑disulfonic acid disodium salt, Indigotine, Brilliant Indigo, 4 G, C.I. Acid Blue 74, C.I. 73015, FD&C Blue 2, Food Blue 1, Sicovit Indigotin 85, E132, Indigo‑5,5′‑disulfonic acid disodium, Indigo‑5,5′-disulphonate sodium salt, 5,5′‑indigodisulfonic acid sodium salt, Indigotindisulfonate sodium, Acid Blue 74, Indigocarmine, Indigo‑5,5′‑disulfonic acid disodium salt, Indigotine, Brilliant Indigo, 4 G, C.I. Acid Blue 74, C.I. 73015, FD&C Blue 2, Food Blue 1, E132, Sicovit Indigotin 85, Indigotine, Indigo Carmine, Indigotindisulfonate sodium, 5,5′‑indigodisulfonic acid sodium salt, Brilliant Indigo, FD&C Blue 2, CI Food Blue 1, Acid Blue 74, CI 73015, Sicovit Indigotin 85, C.I. Pigment Blue 63, CI 75781, Natural Blue 2, Indigo Carmine, CI Blue No. 1 Food Color

Indigotine is an organic compound that is a reddish-blue food additive.
Naturally, Indigotine is derived from sea snails and plants belonging to the genus Indigofera.
Production from organisms is not cost-effective because thousands of sea snails or plants are required to produce a pound of indigotine.

Hence, the synthetic process of producing indigotine though benzene ammonification and aniline sulfonation is cost-effective.
Indigotine (Indigo Carmine, E132 / FD&C Blue 2) is a versatile, water-soluble dye used across food, medical, and industrial fields.
Indigotine has well-documented safety and handling profiles but requires precautions due to potential irritant and sensitizing effects, as well as cardiovascular risks upon intravenous administration.

Indigotine is an organic compound commonly used as a reddish blue food dye.
Indigotine is currently approved for use in the U.S., Canada, and the E.U.
There aren’t that many foods that need to be dyed blue.

The common use of Indigotine cases are just what you might expect: confectionaries (candies), cereal, and other “junk” food.
Two examples are: Froot Loops and Skittles.
Indigotine is a versatile, water-soluble blue dye used across food, medical, lab, and industrial sectors.

While generally approved and stable, Indigotine requires careful handling due to potential irritant, allergenic, and physiological effects—especially upon injection or inhalation.
Indigotine, or 5,5′-indigodisulfonic acid sodium salt, is an organic salt derived from indigo by aromatic sulfonation, which renders the compound soluble in water.

Like indigo, Indigotine produces a blue color, and is used in food and other consumables, cosmetics, and as a medical contrast agent and staining agent; it also acts as a pH indicator.
Indigotine is approved for human consumption in the United States and European Union.
Indigotine has the E number E132, and is named Blue No. 2 by the US Federal Food, Drug, and Cosmetic Act.

Indigotine or Indigotindisulfonate Sodium is an organic compound derived from Indigo using aromatic sulfonation.
The sulfonation renders the compound’s solubility in water.

Indigotine is also called Indigotindisulfonate sodium, 5,5’-indigodisulfonic acid sodium salt, E132, Sicovit Indigotin 85, Food Blue 1, FD&C Blue 2, ci 73015, 4 G, C.I. Acid Blue 74, Brilliant Indigo, and Indigotine.
In medicine, Indigotine's most well-known use is as a diagnostic agent for kidney function tests.

Indigotine, also known as Indigo carmine or FD&C Blue No. 2, is a synthetic blue dye.
Indigotine's designated as E132 in the European Union's food additive numbering system.

Derived from indigo, a naturally occurring dye, indigotine is produced through a chemical synthesis process.
Its intense blue color makes Indigotine a popular choice for various food and other applications.

USES and APPLICATIONS of INDIGOTINE:
Food Additive: Indigotine is approved as E132/FD&C Blue 2 in the US, EU, and elsewhere.
Medical Use: Contrast dye during surgeries (e.g., urology, obstetrics to detect leaks); marketed as Bludigo.
Indigotine is used mucosal staining in endoscopy/surgery.

Laboratory & Industrial uses of Indigotine: pH and redox indicator.
Indigotine is used ozone/superoxide detection in analytical chemistry.
Indigotine is used in cosmetics, inks, dyes, capsules.

Indigotine Is A Synthetic Color, Although 
Indigotine is used To Be Extracted From Plants Of The Genus Indigofera.
Indigotine is used In Coatings, Ice Creams, And Confectionary.

Food & Beverage: Indigotine is approved dye in foods/drinks (E132/FD&C Blue No. 2).
Medical uses of Indigotine: Contrast agent in urology & obstetrics (to detect urinary tract/gut leaks).
Indigotine is used mucosal staining in endoscopy/surgery.

pH Indicator: Indigotine changes from blue to yellow between pH 11.5–14.
Laboratory/Industrial uses of Indigotine: Biological stain (microbiology, histology).
Indigotine is used inks, dyes, sensors, batteries, cosmetics, detergents.

Indigotine is also used as a food colourant, a histological dye and a two-colour pH indicator.
Indigotine (indigotindisulfonate sodium) Injection is a diagnostic agent that tests for renal function used to find ureteral orifices during cystoscopy and ureteral catheterization.

Indications and Usage for Indigotine: Originally employed as a kidney function test, the chief application of Indigotine at present is localizing ureteral orifices during cystoscopy and ureteral catheterization.
Indigotine was originally used as a kidney function test, but it is now mostly used to locate ureteral orifices during cystoscopy and ureteral catheterization.

-Indigotine is used as a positive electrode material
An experiment proves the electric nature of Indigotine.

In glucose which is known as reducing sugar and in the presence of a strong base like sodium hydroxide it reacts to form something called a glucoside anion which wants to donate a pair of electrons these electrons are then picked up by the ICN which first reduces it to a red form and then to a yellow one.
Thus, Indigotine will work as a positive-electrode material that is not solely lithium, but additionally a sodium-electrolyte.

-Indigotine is used as a food additive:
Indigotine gives a very rich blue colour in water.
And as a food additive, Indigotine is also approved in the US and Europe.
In the US and Canada, Indigotine is referred to as FD&C blue number two or just blue – and in Europe, it’s a 132.

-Indigotine is used as an indicator:
Indigotine in a 0.2% aqueous solution is blue at pH 11.4 and yellow at 13.0, thus acting as a pH indicator.

Indigotine also serves as a redox indicator, turning yellow upon reduction.
Through the conversion to isatin-5-sulfonic acid, Indigotine can also be used as a dissolved ozone indicator.

Indigotine is contained in each 5 mL ampule to permit accurate withdrawal and administration of the full dose.
Indigotine gives a deep blue solution when dissolved in water.

-Indigotine - Clinical Pharmacology:
Indigotine is excreted largely by the kidneys, retaining its blue color during passage through the body.
Elimination of the dye begins soon after injection, appearing in the urine within 10 minutes in average cases.

The biological half-life is 4 to 5 minutes following intravenous injection.
Larger quantities are necessary when intramuscular injection is employed.
Appearance time and elimination are delayed following intramuscular injection.

-Uses of Indigotine:
Indigotine is a colourant, which is clinically used for distinctive purposes.
As Indigotine belongs to a class of drugs called Miscellaneous Diagnostic Dyes it can be used alone or with other medications.

-In Clinical Endoscopy:
Endoscopic dye spraying of the gastrointestinal tract (chromoendoscopy) was initially described in 1976.
Indigotine could be a distinction dye that neither reacts with nor is absorbed by the mucosa, however merely pools within the tissue layer grooves and pits permitting higher topographic definition.

In conjunction with improved colonoscopic equipment, this has the potential to boost the diagnostic yield by detective work on unnoticeable lesions which may otherwise be overlooked.

This may be notably vital in surveillance in ulcerative colitis wherever the first changes of abnormalcy will be delicate.
The study showed that the routine use of ICN dye spray throughout the complete colon is straightforward, feasible, and safe.

-Indigotine Injection:
The solution of Indigotine (indigotindisulfonate) is given intravenously or intramuscularly, and its appearance at the ureteral orifices is monitored using the cystoscope.
The recommended initial dosage is an ampoule of 5ml having 40 mg of Indigotine, each mL containing 8 mg of Indigotindisulfonate Sodium and Water for Injection q.s.

The adjustment of pH is done when necessary with Citric Acid and/or Sodium Citrate.
The sterility and non-pyrogenicity should be maintained.

-Indigotine (pH indicator)
Below pH 11.4, Indigotine is blue; above pH 13.0, it is yellow.
Indigotine in a 0.2% aqueous solution is blue at pH 11.4 and yellow at 13.0.

Indigotine is also a redox indicator, turning yellow upon reduction.
Another use is as a dissolved ozone indicator through the conversion to isatin-5-sulfonic acid.

This reaction has been shown not to be specific to ozone: Indigotine also detects superoxide, an important distinction in cell physiology.
Indigotine is also used as a dye in the manufacturing of pharmaceutical capsules.

-Medical uses of Indigotine:
Indigotine, sold under the brand name Bludigo, is used as a contrast agent during surgical procedures.
Indigotine is indicated for use in cystoscopy in adults following urological and gynecological procedures.
Indigotine was approved for medical use in the United States in July 2022.

-In obstetric surgery, Indigotine may be used to detect amniotic fluid leaks.
In urologic surgery, intravenous Indigotine can be used to highlight portions of the urinary tract.
The dye is filtered rapidly by the kidneys from the blood, and colors the urine blue.
However, the dye can cause a potentially dangerous acute increase in blood pressure in some cases.

-Indigotine stain is not absorbed into cells, so it is applied to tissues to enhance the visibility of mucosa.
This leads to Indigotine's use for examination and diagnosis of benign and malignant lesions and growths on mucosal surfaces of the body.

-Food, pharmaceutical, cosmetic, and scientific uses ofIndigotine:
Indigotine is one of the few blue food colorants.
Others include the anthocyanidins and rare substances such as variagatic acid and popolohuanone.

-Industrial Uses of Indigotine
Beyond food, indigotine finds application in various industrial sectors.
Indigotine is used as a dye in pharmaceuticals, cosmetics, and textiles.

Indigotine also serves as a pH indicator in some chemical processes and as a diagnostic tool in medical procedures.
Furthermore, indigotine has applications in the printing industry, specifically in inkjet inks.

-Food Applications of E132
According to EFSA, Indigotine is permitted in a range of food products within the EU.
These include confectionery, baked goods, dairy products, beverages, and certain processed foods.

Indigotine's primary function is to enhance or restore the blue color of food products, making them more visually appealing.
EFSA has established an Acceptable Daily Intake (ADI) of 5 mg/kg body weight for indigotine.

This ensures that the amount consumed through food remains within safe limits.
EFSA's 2010 reassessment of indigotine provides further details on its permitted uses and safety evaluation.

-Non-Food Uses of Indigotine:
Indigotine is used as a pH indicator.
Indigotine is blue at pH 11.4 and yellow at 13.0.

Indigotine is used in obstetrics to help detect amniotic fluid leaks.
Indigotine is used during surgery to highlight the urinary tract and help to detect leaks.

-Common Uses of Indigotine:
Indigotine is distinguished by its rich royal blue color, and can be used for coloring foods and drugs, including dietary supplements, blueberry bagels, breakfast cereals, cakes and cupcakes, candies including chocolate, chewing gum, dairy products, decorations for baking, frozen treats, and sauces and seasonings.

-Food Use and Applications of Indigotine:
Indigotine is a food additive that has been approved in the United States, Europe, and Australia.
The joint committee of the World Health Organization and the Food and Agricultural Organization has established an acceptable daily level of indigotine intake as a food additive.

The common foods colored with indigotine are cereals, candies, and cakes (Saltmarsh 2013).
Since indigotine is soluble in water, it is an appropriate food colorant, which provides a uniform coloring in diverse foods.

In addition to coloring food, indigotine has numerous uses.
In medicine, indigotine is an analytic agent used in the diagnosis of renal function by detecting orifices through cystoscopy and catheterization.

Moreover, it detects leakage of amniotic fluid in pregnant women.
In the laboratory, indigotine is used as a pH indicator for it turns yellow at a pH of 13 and blue at a pH of 11.4.
Although heat does not influence the color of indigotine, oxygen and light decolorize it, whereas pH influences its color.

BENEFITS & FUNCTIONS OF INDIGOTINE:
*Indigotine is a stable and vibrant blue dye for food, cosmetics, lab reagents.
*Indigotine enables diagnostic visualization in medical procedures.
*Indigotine functions as a useful pH/redox indicator and in analytical chemistry.

PRODUCTION OF INDIGOTINE:
Indigotine isn't directly extracted from natural indigo.
Instead, it's synthesized through a multi-step chemical process that involves sulfonation of indigo.
This process creates a water-soluble form of the dye, making Indigotine suitable for various applications.
The final product is a dark blue powder that dissolves readily in water, producing a vibrant blue solution.

ORIGIN OF INDIGOTINE:
Blue dye, which occurs naturally in the shrub Indigofera tinctoria, but commercially Indigotine is prepared synthetically.

MANUFACTURE AND SPECIFICATIONS OF INDIGOTINE:
Raw materials required for the synthesis of Indigotine are benzene, formaldehyde, ammonia, sodium hydroxide, sodamide, potassium hydroxide, and sulfuric acid.

The synthesis of Indigotine occurs in five stages, which entail the formation of phenylglycine, the fusion of molten mixture, the oxidation of indigo, the acidification of indigo, and the purification of Indigotine.

The formation of phenylglycine is the first stage involves the combination of benzene, ammonia, and formaldehyde.
In the second stage, which is the fusion stage, sodamide, phenylglycine, sodium hydroxide, and potassium hydroxide reacts in high temperatures of 500°C to form indoxylate salts.

In the third stage of oxidation, indoxylate salts convert into indigo under alkaline conditions, 70°C, and ammonia pressure.
Subsequently, acidification with 30% sulfuric acid to form indigotine occurs in the fourth stage.
To remove contaminants, which are mainly alkali salts, ammonium salts, and sulfuric acid, indigotine is boiled with pyridine and hydrochloric acid.

NAME AND STRUCTURE OF INDIGOTINE:
The chemical (IUPAC) name of Indigotine is 3,3′-dioxo-2,2′-bisindolyden-5,5′-disulfonic acid disodium salt.
Other synonyms of Indigotine are brilliant indigo, indigo carmine, FD&C-blue-2, CI food blue 1, and sicovit indigotin 85 (Food and Agricultural Organization 2010).

Indigotine has a chemical formula of C16H8N2Na2O8S2, a molecular mass of 466.36 g/mole, and a molecular structure is shown in Figure 1 below.
Physical properties show that Indigotine is a blue or purple powder that is soluble in water with a melting point of 300°C.
Indigotine is classified as a food colorant and assigned a code number 132 in the range of blue and violet colors (Federal Register of Legislation 2018).

BENEFICIAL PROPERTIES (LIMITED) OF INDIGOTINE:
While the primary role of indigotine is as a colorant, some research suggests potential benefits.
For example, Indigotine has been investigated for its potential antioxidant properties in certain contexts.
However, these are not the primary reasons for Indigotine's use, and more research is needed to confirm these potential benefits.
Indigotine's crucial to remember that its primary function is aesthetic and not nutritional.

PHYSICAL DESCRIPTION OF INDIGOTINE:
Indigotine occurs as a blue-brown to red-brown powder or as granule.
Indigotine is an indigoid dye, consisting of a mixture of disodium 3,3′-dioxo-[delta2,2′-biindoline]-5,5′-disulfonate (the principal component), disodium 3,3′-dioxo-[delta2,2′-biindoline]-5,7′-disulfonate (an isomer) and subsidiary coloring matters and may be converted to the corresponding aluminum lake.

SYNTHETIC PRODUCTION OF INDIGOTINE:
Indigo (or indigo paste) is synthetically produced by first using aniline (which is produced from benzene) and formaldehyde to create molecules called N-phenylglycine.
These molecules are then fused in a molten mixture of sodamide and sodium and potassium hydroxides under ammonia pressure.

The indigo is then isolated and purified.
Once the indigo has been produced, it is heated in the presence of sulphuric acid.
Indigotine is then isolated and subjected to purification procedures.

APPLICATIONS & BENEFITS OF INDIGOTINE:
Indigotine enables diagnostic visualization in medical procedures (e.g., urinary tract, mucosal diagnostics).
Indigotine provides a stable blue dye in foods, medical devices, cosmetics, and lab reagents.
As a pH indicator, Indigotine’s effective in alkaline ranges for chemical titrations and quality control.

DOSAGE FOR INDIGOTINE:
Indigotine solution is injected either intravenously or intramuscularly, and its appearance at the ureteral orifices is watched with the cystoscope in place.
The intravenous method is preferred because a 5 mL injection is sufficient.

WHAT DRUGS, SUBSTANCES, OR SUPPLEMENTS INTERACT WITH INDIGOTINE?
Indigotine may interact with other drugs.
Tell your doctor all medications and supplements you use.

INDIGOTINE DURING PREGNANCY OR BREASTFEEDİNG:
Indigotine During Pregnancy or Breastfeeding
During pregnancy, Indigotine should be used only if prescribed.
Indigotine is unknown if this drug passes into breast milk.
Consult your doctor before breastfeeding.

SAFETY HANDLING & FIRST-AID OF INDIGOTINE:
Personal Protection: 
Use gloves, goggles, lab coat; avoid dust/aerosols; use ventilation, respirator for dust.

Storage:
Store tightly sealed, dry, cool, light-protected.

Spill Cleanup: 
Dampen powder before cleaning; contain and dispose as chemical waste; wash surfaces thoroughly.

Fire Safety: 
Non-flammable solid; may emit toxic fumes (SOx, NOx); extinguish with dry chemical, CO₂, or foam.

Eye Contact: Flush 15–30 min with water; get medical eye exam.

PHYSICAL and CHEMICAL PROPERTIES of INDIGOTINE:
CAS Number: 860‑22‑0 
EC Number: 212‑728‑8 
Molecular Formula: C₁₆H₈N₂Na₂O₈S₂ 
Molar Mass: ~466.36 g/mol 
Appearance: Dark blue–purple crystalline powder or solid 
Melting Point: Above 300 °C 
Solubility: Approx. 10 g/L in water at 25 °C; slight ethanol solubility 
pH Indicator: Blue at pH ~11.4, shifts to yellow at pH ~13 
UV‑Vis λ_max: ~608 nm 

Stability: Stable under normal conditions; degraded by strong oxidizers, light sensitive 
orgchemboulder.com
Other: Powder odorless; pH near neutral in solution
E Number: E132
Colour Index ™ Name: Food Blue 1
Colour Index ™ Number: CI 73015
CAS Number: 860-22-0

EC Number: 212-728-8
CAS Number: 860-22-0
EC Number: 212-728-8
E Number: E132
MDL Number: MFCD00005723
PubChem CID: 2723854
PubChem Substance ID: 87571590
Reaxys Registry Number: 905434
Merck Index (14th Ed): 4944

Colour Index: 73015
HS Code: 3212 90 90
IUPAC Name: disodium (E)-3,3'-dioxo-1H,1'H,3H,3'H-[2,2'-biindolylidene]-5,5'-disulfonate
Molecular Formula: C16H8N2Na2O8S2
Molecular Weight: 466.36 g/mol
Exact Mass: 466.36 Da
Appearance: Dark blue to purple crystalline powder or solid
Color (aqueous solution): Neutral pH – blue; 
acidic pH – violet-blue; 
alkaline pH (11.5–14) – yellow

Melting Point: >300 °C (some sources >340 °C)
Density: ~0.71 g/cm³ (29 °C)
Bulk Density: 700–900 kg/m³
Refractive Index: 1.335 (n²⁰/D)
Solubility: Water: ~1 g/100 mL (10 g/L) at 25 °C
Slightly soluble in ethanol
pH: Neutral (pH ~7 at 10 g/L)

LogP: –3.57 (hydrophilic)
UV-Vis Absorption: λ_max ≈ 608 nm
Absorption Ratio P-15/P+15: 0.98 to 1.07
Dye Content: ≥80%
Stability: Stable under normal conditions; sensitive to light and strong oxidizers
SMILES: [Na+].[Na+].[O-]S(=O)(=O)C1=CC=C2NC(C(=O)C2=C1)=C1NC2=CC=C(C=C2C1=O)S([O-])(=O)=O
InChI Key: KHLVKKOJDHCJMG-QDBORUFSSA-L
Storage: Keep in a cool, dark place; avoid light exposure.

FIRST AID MEASURES of INDIGOTINE:
-Description of first-aid measures
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation: 
Fresh air.
*In case of skin contact: 
Take off immediately all contaminated clothing. 
Rinse skin with
water/ shower.
*In case of eye contact:
After eye contact: 
Rinse out with plenty of water. 
Call in ophthalmologist. 
Remove contact lenses.
*If swallowed:
After swallowing: 
Immediately make victim drink water (two glasses at most). 
Consult a physician.
-Indication of any immediate medical attention and special treatment needed.
No data available

ACCIDENTAL RELEASE MEASURES of INDIGOTINE:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains. 
Collect, bind, and pump off spills. 
Observe possible material restrictions. 
Take up dry. 
Dispose of properly. 
Clean up affected area.

FIRE FIGHTING MEASURES of INDIGOTINE:
-Extinguishing media:
*Suitable extinguishing media:
Carbon dioxide (CO2) 
Foam 
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of INDIGOTINE:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection. 
Safety glasses
*Body Protection:
protective clothing
*Respiratory protection:
Recommended Filter type: Filter A 
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of INDIGOTINE:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed. 
Dry.

STABILITY and REACTIVITY of INDIGOTINE:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature).
-Possibility of hazardous reactions:
No data available