66108-95-0

Hazard Information

Chemical Properties

White Solid

Definition

ChEBI: A benzenedicarboxamide compound having N-(2,3-dihydroxypropyl)carbamoyl groups at the 1- and 3-positions, iodo substituents at the 2-, 4- and 6-positions and an N-(2,3-dihydroxypropyl)acetamido group at the 5-position.

Brand name

Omnipaque (GE Healthcare).

General Description

Iohexol is a low-osmolar, nonionicmonomer with 46% iodine content. Iohexol is one ofthe few iodinated contrast agents indicated for intrathecaluse (myelography). Only selected concentrations of theproduct have this indication. Besides myelography, iohexolfinds widespread use in excretory urography, angiography,and CT procedures. Specific concentrations may have additionalindications in adults and/or children for arthrography,hysterosalpingography, endoscopic retrograde pancreatography,cholangiopancreatography, herniography, voidingcystourethrography, oral pass-thru examination of the GItract or CT of the abdomen.

Synthesis

31127-80-7

106-89-8

66108-95-0

92339-11-2

N1,N3-bis(2,3-dihydroxypropyl)-5-(N-(2,3-dihydroxypropyl)acetamido)-2,4,6-triiodomethylbenzene dicarboxamide (Compound A, 1120.5 kg, 1.50 kmol) and 1-chloro-2,3-propylene oxide were synthesized as 5-(acetamido)-N,N'-bis(2,3-dihydroxypropyl)-5-(N-(2,3-dihydroxypropyl)acetamido)-2,4,6- Triiodo-m-toluene dicarboxamide and 5,5'-((2-hydroxypropyl-1,3-diyl)bis(acetylazanediyl))bis(N1,N3-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-m-toluene dicarboxamide) in the following general steps: 1. dissolve compound A (1120.5 kg, 1.50 kmol) in a solution of water (1232.6 kg) containing KOH (140.0 kg, 2.25 kmol), controlling the temperature below 20 °C. 2. boric acid (64.9 kg, 1.05 kmol) and hydrochloric acid (30.4 kg, 0.30 kmol) were added in batches. 3. 1-chloro-2,3-epoxypropane (83.3 kg, 0.90 kmol) was added slowly and dropwise, keeping the pH of the reaction system between 10-11. 4. The progress of the reaction was monitored by HPLC during the reaction. 5. When the content of compound A was below 5%, the reaction was quenched by addition of water (1232.6 kg) and the pH was adjusted to 5-6 with 18% hydrochloric acid. 6. The reaction mixture was decolorized by activated carbon and filtered. 7. HPLC analysis showed that the filtrate contained 86.3% iodixanol, 7.5% iodohexanol, 2.9% compound A and 2.7% O-alkylation by-products and other impurities.

storage

4°C, protect from light

References

[1] Patent: WO2011/63551, 2011, A1. Location in patent: Page/Page column 15-16
[2] Patent: EP2277853, 2011, A1. Location in patent: Page/Page column 7
[3] Patent: EP2277852, 2011, A1. Location in patent: Page/Page column 7
[4] Acta Chemica Scandinavica, 1995, vol. 49, # 6, p. 446 - 456
[5] Patent: US2011/21823, 2011, A1. Location in patent: Page/Page column 2-3

Material Safety Data Sheet(MSDS)

Questions And Answer

• Non-ionic contrast agent

  Iohexol is a non-ionic contrast agent with its pure product appearing as white or light gray powder and having hygroscopicity. In the early 80s of last century, it has been successfully developed by the Nycomed Company (Norwegian) and has first entered into market in 1982 in Norway and Sweden. In 1985, it has obtained the approval of the US Food and Drug Administration (FDA) for entering into US market; in the early 90s, Schering AG and Japan's first pharmaceutical Co., Ltd. were respectively subject to transferee production with product sales in Europe and the Asia-Pacific countries.
  The six hydroxyl groups in its molecules are evenly distributed around the benzene ring, effective shielding the lipophilic iodobenzene ring, making it have high hydrophilic, low viscosity, low permeability than ordinary ion-type contrast agent and low toxicity against the nerve system, etc. It is the raw material for the production of water-soluble, non-ionic X-CT contrast agent in pharmaceutical factory. Iohexol is also currently one of the best contrast agents. The developed countries have completely used it to replace ionography agent. It is suitable for myelography, cardiovascular, arteriovenous, lymphatic system, urography and enhanced CT scan. The general dosage is as follows: decision regarding spinal canal imaging is based on the location; lumbar thoracic 24% solution: 8~12ml, neck 24% solution: 10~15ml, CT scan Cisternography 8~12ml.;

• Pharmacological effects

  Iohexol contrast agent belongs to non-ionic water-soluble contrast agent with a similar osmotic pressure with plasma as well as moderate viscosity. It is easily for injection. Clinical angiography and urography have proved less toxic than ionic contrast agents, and can be safely used for myelography. The reason is that the non-ionic contrast agent has weak stimulation on the mast cell with less histamine release and less likely to cause allergic reactions. This product is weak vasodilator, not easy to cause hypotension; it causes very small injury on vascular endothelium, difficult to form thrombosis; small effect on heart and kidney function. It has a lower toxicity than amikacin. This product almost does not penetrate the cell membrane. After intravenous injection, it is mainly distributed in the interstitial cavity without being absorbed by organ and tissue. It is not metabolized by the body and is released mostly with the urine in the prototype form. PBP is smaller than 20%.
  Non-ionic intravascular contrast agents: such as iobitridol, ioversol, iodohexol, iopamidol, iopromide and iodixanol.
  ;

• Clinical application

  It can be used for angiography, urography, cerebral angiography, peripheral and various kinds of arterial angiography, venography, digital subtraction and CT enhanced scan. Myelography and the use of subarachnoid injection for brain pool CT scan. It can also be applied to various kinds of body cavity examinations.
  Subarachnoid space application
  ①It should be done of iodine allergy test before the application. Patients of positive result should be disabled. Patients of a history of epilepsy should be disabled.
  ②Patients having a history of allergies or being suspected allergic to this product, but must be subject to the angiography of this product can choose to apply adrenal cortex hormones and antihistamines before the contrast to prevent. But the spinal cord should be disabled of applying adrenal corticosteroid drugs.
  ③Patients of local or systemic bacterial infection should not carry out lumbar puncture, of course, can’t use this product for angiography.
  ④If necessary, it can be given of sedation agents such as diazepam before surgery. Upon severe pain, it can be administrated of analgesics.
  ⑤Good body fluid condition can reduce the incidence of adverse reactions, therefore it should be prevented of dehydration of patients.
  ⑥After angiography, allow the patients to sit in bed. The head should be elevated for at least 6 hours. The patient should maintain the supine position for 24 hours without self-move or bending down to prevent the residual contrast agent from flowing into the brain and reduce the leakage of cerebrospinal fluid.
  ⑦If the patients get nausea, vomiting, it should be applied of intravenous fluids to replace the fluid food; if necessary, it should be given of antiemetic.
  ⑧Upon myelography failure, it is not appropriate for immediate repeated angiography.
  ⑨Upon seizures, it should be immediately applied of intravenous injection of 10mg diazepam. To prevent recurrence of epilepsy, it can be applied of intramuscular injection of 0.2 g phenobarbital sodium at 20 to 30 minutes after the stopping of pathogenesis.
  ⑩The relative density of iohexol injection should be higher than that of cerebrospinal fluid.;

• Intravascular applications

  ①Before use, it should be applied of allergy testing. Positive patients should be disabled.
  ②Patients having a history of allergy, being allergic to iodine, of asthma should be disabled or used with caution.
  ③Patients of severe liver and kidney dysfunction, severe thyroid disease, bone marrow leukemia should be used with caution; These patients should be disabled upon dehydration. Patients of diabetes having a serum creatinine concentration of more than 0.5mmol /L should be disabled.
  ④pregnant women should be used with caution. Under conditions that it must be applied, it should be used of the lowest dose.
  ⑤This product can interfere with thyroid function tests, so that the ability of thyroid tissue  binding to iodine will be reduced, and it should be taken of several days or even two weeks for fully recover.
  ⑥contrast agent should not be mixed with other drugs for compatibility, instead should be used of a dedicated syringe.;

• Dosage and Usage

  Intrathecal injection: Dose should be according to the check project and the usage technical decisions. It can be referred to the following table.
  
  Application items

  Concentration (mg/ml)

  Usage amount (ml/per time)

  Waist, thoracic
  angiography

  180
  240

  0~15
  8~12

  Cervical angiography
  CT scan Cisternography

  240
  180
  240

  10~12
  5~15
  4~12

  Myelography for children

   

   

  <2 years old
  2～6 years old
  >6 years old

  180
  180
  180

  2~6
  4~8
  6~12
  It can be used for cardiovascular, arterial intravenous and urinary tract radiography. The iodine concentration and dosage used should be generally the same as other angiographic contrast agents currently used.;

• Medicine interactions

  1, Patients subjecting to metformin treatment, if subjecting to simultaneous injection of iohexol contrast agent, may get lactic acidosis and acute renal failure.
  2, Simultaneous administration of tricyclic antidepressants or monoamine oxidase inhibitors during the intrathecal injection of the drug can reduce the threshold of seizures, and lead to seizures.
  3. Patients treated with interleukin-2 within 2 weeks had an increased risk of delayed response (cold-like symptoms and skin reactions).
  4, Ⅲ antiarrhythmic drugs such as amiodarone, in the recommended dose, can extend the QT interval. The effect of prolonging the QT interval when combined with this product has additive effect.
  This information was edited by Chemicalbook (2015-08-03).;

• Adverse effects

  1. Adverse effects after application in subarachnoid space are generally the same as that of receiving the lumbar puncture, but are mostly mild. The incidence of headache is less than that of using meglumine. Severe headache lasting several days may be intermittent. Other may have nausea, vomiting, dizziness, neck back pain, limb pain and paresthesia. EEG showed no clear short wave.
  2. Adverse effects after intravascular administration were significantly lower than those of other ionic contrast agents in frequency and severity, and adverse reactions were similar to that of meglumine. A small number of patients have mild reactions, such as warm feeling, red, nausea, vomiting, mild chest pain, skin itching, urticaria, numbness and lower limbs.;

• Precautions

  1, Patients with allergic history to iodine and allergic constitution should take with caution.
  2, Patients of liver and kidney dysfunction, heart and circulatory system dysfunction, physical weakness, cerebral arteriosclerosis, diabetes, goiter and leukemia should take with caution.
  3, Patients of severe hyperthyroidism should be disabled.
  4, generally it should be prepared well of acute allergic reactions rescue.
  Chemical properties
  It appears as white or light gray powder with hygroscopicity.;

• Uses

  It is the raw material for the production of water-soluble, non-ionic X-CT contrast agent in pharmaceutical factory. The trade name of this contrast agent is Omnipaque. This contrast agent is usually injected into the vein before CT angiography to be used for angiography, urinary system, spinal cord and joint, lymphatic system angiography, with advantages of low contrast density, low toxicity and good tolerance type. Iohexol is also currently one of the best contrast agents. The developed countries have completely used it to replace ionography agent. It is also a diagnostic drug.
  It can be used as non-ionic X-CT contrast agent.;

Spectrum Detail

Well-known Reagent Company Product Information

Supplier

Related Products