MRI Contrast agent
This contrast agent does not target specific biological receptors or enzymes. It is a non-specific paramagnetic gadolinium complex that acts by shortening the longitudinal relaxation time (T1) of tissues, producing brighter signals in MRI images. It distributes in the extracellular space and is excreted unchanged via the kidneys. Its primary "target" is the water protons in tissues, where it enhances relaxation rates through dipole-dipole interactions between the unpaired electrons of Gd³⁺ and the protons of water molecules.

Gadoterate Meglumine is a gadolinium chelate paramagnetic contrast agent. When placed in a magnetic field, gadoterate meglumine produces a large magnetic moment and so a large local magnetic field, which can enhance the relaxation rate of nearby protons; as a result, the signal intensity of tissue images observed with magnetic resonance imaging (MRI) may be enhanced. Because this agent is preferentially taken up by normal functioning hepatocytes, normal hepatic tissue is enhanced with MRI while tumor tissue is unenhanced. In addition, because gadobenate dimeglumine is excreted in the bile, it may be used to visualize the biliary system using MRI.

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In vitro, gadoterate meglumine demonstrates high thermodynamic stability, apparent stability, and kinetic stability, partly due to its macrocyclic structure, which contributes to a more favorable safety profile. It is used in imaging of the central nervous system (brain and spinal cord), abdomen, pelvic organs, breast, bones and joints, angiography, and cardiac electrophysiology. The compound shows no significant in vitro biological activity beyond its paramagnetic properties for MRI contrast enhancement.

Therapeutic Uses
No DOTAREM dosage adjustment is recommended for patients with renal impairment. Gadoterate meglumine can be removed from the body by hemodialysis.
In clinical studies of DOTAREM, 900 patients were 65 years of age and over, and 312 patients were 75 years of age and over. No overall differences in safety or efficacy were observed between these subjects and younger subjects. In general, use of DOTAREM in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. No age-related dosage adjustment is necessary.
The safety and efficacy of DOTAREM at a single dose of 0.1 mmol/kg have been established in pediatric patients from 2 to 17 years of age. No dosage adjustment according to age is necessary in this population. The safety and efficacy of DOTAREM have not been established in pediatric patients below 2 years of age. GFR does not reach adult levels until 1 year of age.
DOTAREM is a gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (2 years of age and older) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

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In vivo, gadoterate meglumine is administered intravenously for MRI contrast enhancement. It distributes throughout the extracellular space and is excreted unchanged by the kidneys. It is used to detect and visualize areas with disruption of the blood-brain barrier (BBB) and/or abnormal vascularity. Its in vivo activity is purely physical (paramagnetic relaxation enhancement) rather than pharmacological, and it does not bind to or modulate any physiological targets.

In vitro enzyme/receptor binding assays are not applicable for this contrast agent as it does not interact with enzymes or receptors. A typical non-cellular protocol for evaluating its properties involves: (1) preparing gadoterate meglumine solutions at various concentrations in water or buffer; (2) measuring T1 and T2 relaxation times using a relaxometer or MRI scanner at different magnetic field strengths; (3) calculating relaxivity values (r1 and r2) from the concentration-dependent relaxation rate; and (4) comparing relaxivity to reference standards to assess contrast enhancement efficiency.

In vitro cell-based assays are not typically performed with gadoterate meglumine as it is not a cytotoxic or biological agent. However, cell viability assays may be conducted to assess biocompatibility: (1) culture relevant cell lines (e.g., HEK-293 or NRK-49F) in appropriate medium; (2) treat cells with gadoterate meglumine at various concentrations (0.1-10 mM) for 24-72 hours; (3) assess cell viability using MTT or CCK-8 assays; (4) measure intracellular gadolinium content by ICP-MS; and (5) evaluate any cytotoxic effects compared to untreated controls.

In vivo animal experiments typically involve pharmacokinetic and imaging studies. A common protocol is: (1) administer gadoterate meglumine intravenously to mice, rats, or rabbits at doses of 0.1-1 mmol/kg; (2) perform MRI scans at multiple time points post-injection (e.g., 5, 15, 30, 60 min); (3) measure signal intensity enhancement in target organs; (4) collect blood and tissue samples at various time points; (5) analyze gadolinium concentration by ICP-MS; and (6) evaluate biodistribution and elimination kinetics.

Absorption, Distribution, and Excretion: Following administration of 0.1 mmol/kg DOTAREM, total gadolinium was primarily excreted in the urine, with 72.9 ± 17.0% excreted in women and 85.4 ± 9.7% in men over 48 hours (mean ± standard deviation). Similar values were achieved after a cumulative dose of 0.3 mmol/kg (0.1 + 0.2 mmol/kg, 20 min later), with 85.5 ± 13.2% and 92.0 ± 12.0% of gadolinium recovered in the urine over 48 hours in women and men, respectively. In healthy subjects, renal clearance and total clearance of total gadolinium were comparable (1.27 ± 0.32 and 1.74 ± 0.12 mL/min/kg for women; 1.40 ± 0.31 and 1.64 ± 0.35 mL/min/kg for men), indicating that the drug is primarily cleared by the kidneys. Within the studied dose range (0.1 to 0.3 mmol/kg), the kinetics of total gadolinium were linear. The steady-state volume of distribution of total gadolinium in normal subjects was 179 ± 26 mL/kg in women and 211 ± 35 mL/kg in men, roughly equivalent to the volume of distribution in extracellular fluid. Calcium gadotate cannot cross the intact blood-brain barrier and therefore does not enhance the visualization of normal brain tissue or lesions with a normal blood-brain barrier (e.g., cysts, mature postoperative scars). However, disruption of the blood-brain barrier or vascular abnormalities can allow calcium gadotate to be distributed in lesions such as tumors, abscesses, and infarctions. It is currently unclear whether DOTAREM is secreted into human breast milk. Limited case reports of gadolinium-based contrast agents used in lactating women suggest that 0.01% to 0.04% of the maternal gadolinium dose is secreted into human breast milk. Because many drugs are excreted into human breast milk, caution should be exercised when administering DOTAREM to breastfeeding women. Nonclinical data show that very small amounts of gadoteric acid meglumine are excreted into breast milk (<0.1% of the intravenous dose) and are poorly absorbed via the gastrointestinal tract.
Metabolism/Metabolites
It is currently unclear whether gadoteric acid is metabolized.
Biological Half-Life
In normal subjects, the pharmacokinetics of total gadolinium following intravenous administration of 0.1 mmol/kg DOTAREM followed a one-compartment open model, with mean elimination half-lives (expressed as mean ± standard deviation) of approximately 1.4 ± 0.2 hours in females and 2.0 ± 0.7 hours in males.

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Pharmacokinetic properties: Gadoterate meglumine is administered intravenously and distributes in the extracellular space. It is not protein-bound and is excreted unchanged by glomerular filtration with a half-life of approximately 1.5-2 hours in patients with normal renal function. The compound has one of the highest thermodynamic and kinetic stabilities among GBCAs. It is not metabolized and is eliminated primarily via the kidneys. In patients with renal impairment, the elimination half-life is prolonged, and caution is advised due to the risk of nephrogenic systemic fibrosis.

Toxicity Overview
Product Introduction: Gadolinium meglumine is a paramagnetic macrocyclic ionic contrast agent used for magnetic resonance imaging. Human Exposure and Toxicity: The most common adverse reaction is headache (1.5%). Adverse reactions occurring in less than 0.2% of patients receiving gadolinium meglumine injections include: chills, rash, drowsiness, fatigue, dizziness, vomiting, pruritus, paresthesia, dysgeusia, extremity pain, anxiety, hypertension, palpitations, oropharyngeal discomfort, elevated serum creatinine, and injection site reactions, including injection site inflammation, extravasation, pruritus, and fever. Gadolinium-based contrast agents (GBCAs) increase the risk of developing renal systemic fibrosis (NSF) in patients with impaired drug clearance. Gadolinium-based contrast agents (GBCAs) should be avoided in these patients unless diagnostic information is critical and cannot be obtained through non-contrast MRI or other examinations. Renal systemic fibrosis (NSF) can lead to fatal or disabling fibrosis affecting the skin, muscles, and internal organs. The risk of NSF is highest in patients with chronic severe kidney disease (glomerular filtration rate (GFR) < 30 mL/min/1.73 m2) or acute kidney injury. Patients should be screened for acute kidney injury and other conditions that may impair kidney function. For patients at risk of chronic kidney impairment (e.g., age > 60 years, hypertension, diabetes), GFR should be estimated by laboratory tests. For patients at the highest risk of NSF, do not exceed the recommended dose of DOTAREM and allow sufficient time for drug clearance before re-administration. Animal studies: Reproductive and developmental toxicity studies of gadotamide meglumine have been conducted in rats and rabbits. Female rats were intravenously administered gadotamide meglumine at doses of 0, 2, 4, and 10 mmol/kg/day (or, based on body surface area, equivalent to 3.2, 6.5, and 16.2 times the recommended human dose, respectively) throughout the mating period up to day 17 of gestation (GD17) 14 days prior to mating. Pregnant rabbits were intravenously injected with gadotium ether meglumine at doses of 0, 1, 3, and 7 mmol/kg/day (or, on a body surface area basis, equivalent to 3.3, 10, and 23 times the human dose, respectively). No effects on embryonic development were observed at doses up to 10 mmol/kg/day in rats and up to 3 mmol/kg/day in rabbits. Maternal toxicity was observed at a dose of 10 mmol/kg/day in rats (equivalent to 16 times the human dose on a body surface area basis) and at a dose of 7 mmol/kg/day in rabbits (equivalent to 23 times the human dose on a body surface area basis).
Interactions
Gadotium ether is a paramagnetic molecule that generates a magnetic moment when placed in a magnetic field. This magnetic moment enhances the relaxation rate of nearby water protons, resulting in increased tissue signal intensity (brightness).
Antidote and Emergency Treatment
/SRP:/ Immediate First Aid Measures: Ensure adequate decontamination has been performed. If the patient stops breathing, begin artificial respiration immediately, preferably using a demand ventilator, bag-valve-mask, or simple breathing mask, and follow the training instructions. Perform cardiopulmonary resuscitation if necessary. Immediately flush contaminated eyes with running water. Do not induce vomiting. If vomiting occurs, tilt the patient forward or place them in the left lateral decubitus position (head down if possible) to maintain an open airway and prevent aspiration. Keep the patient calm and maintain normal body temperature. Seek immediate medical attention. /Class A and Class B Poisoning/
/SRP:/ Basic Treatment: Establish a patent airway (using an oropharyngeal or nasopharyngeal airway if necessary). Suction if necessary. Observe for signs of respiratory failure and provide assisted ventilation if necessary. Administer oxygen using a non-invasive breathing mask at a flow rate of 10 to 15 liters per minute. Monitor for pulmonary edema and treat as necessary… Monitor for shock and treat as necessary… Anticipate seizures and treat as necessary… If eyes are contaminated, rinse immediately with water. During transport, continuously rinse each eye with 0.9% saline… Do not use emetics. In case of ingestion, rinse mouth and dilute with 5 mL/kg to 200 mL of water, provided the patient is able to swallow, has a strong gag reflex, and does not drool… After decontamination, cover skin burns with a dry, sterile dressing… /Class A and B Poisons/
/SRP:/ Advanced Treatment: For patients with impaired consciousness, severe pulmonary edema, or severe respiratory distress, consider oropharyngeal or nasopharyngeal endotracheal intubation to control the airway. Positive pressure ventilation using a bag-valve-mask may be effective. Consider medical treatment for pulmonary edema… Consider the use of a β-receptor agonist (such as salbutamol) for severe bronchospasm… Monitor heart rhythm and treat arrhythmias as necessary… Initiate intravenous infusion of 5% glucose solution (D5W TKO) /SRP: “Keep patent,” minimum flow rate/. If signs of hypovolemia appear, administer 0.9% normal saline (NS) or lactated Ringer's solution (LR). Use caution with fluid administration for hypotension accompanied by signs of hypovolemia. Watch for signs of fluid overdose… Use diazepam or lorazepam to treat seizures… Use promecaine hydrochloride to assist eye irrigation… /Toxins A and B/ Currance, PL Clements, B., Bronstein, AC (eds.); Emergency care for exposure to hazardous substances. 3rd edition revised, Elsevier Mosby, St. Louis, Missouri, 2007, p. 10. 160-1
Human Toxicity Excerpt
/Human Exposure Studies/ In healthy volunteers and patients, the tolerability of DOTAREM at cumulative doses up to 0.3 mmol/kg was similar to that at lower doses.
/Signs and Symptoms/ During the clinical trial, 141 pediatric patients (7 < 24 months, 33 2–5 years, 58 6–11 years, and 43 12–17 years) received DOTAREM. Overall, 6 pediatric patients (4.3%) reported at least one adverse reaction after receiving DOTAREM. The most common adverse reaction was headache (1.5%). Most adverse events were mild and short-lived, and all patients recovered without treatment.
/Signs and Symptoms/ Adverse reactions occurring in less than 0.2% of patients receiving DOTAREM included: chills, rash, somnolence, fatigue, dizziness, vomiting, pruritus, paresthesia, dysgeusia, limb pain, anxiety, hypertension, palpitations, oropharyngeal discomfort, elevated serum creatinine, and injection site reactions, including injection site inflammation, extravasation, pruritus, and fever.
/Other Toxicity Information/ Gadolinium-based contrast agents (GBCAs) increase the risk of developing renal systemic fibrosis (NSF) in patients with impaired drug clearance. GBCAs should be avoided in these patients unless diagnostic information is critical and cannot be obtained via non-contrast MRI or other examinations. Renal systemic fibrosis (NSF) can lead to fatal or disabling fibrosis affecting the skin, muscles, and internal organs. High-risk groups for NSF include patients with chronic severe kidney disease (glomerular filtration rate < 30 mL/min/1.73 m²) or acute kidney injury. Patients should be screened for acute kidney injury and other conditions that may impair kidney function. For patients at risk of chronic renal impairment (e.g., age > 60 years, hypertension, diabetes), glomerular filtration rate (GFR) should be estimated by laboratory tests. For patients at high risk of renal systemic fibrosis (NSF), do not exceed the recommended DOTAREM dose and allow sufficient time for drug clearance before re-administering.
Non-human toxicity excerpt
/Experimental animals: Developmental or reproductive toxicity/ In rats or rabbits, no effects on embryonic or fetal development were observed at doses up to 10 mmol/kg/day or 3 mmol/kg/day. The doses in rats and rabbits were 16 and 10 times the recommended human dose based on body surface area, respectively. DOTAREM should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus.
/Experimental animals: Neurotoxicity/ Reproductive and developmental toxicity studies of gadotamide meglumine have been conducted in rats and rabbits. Female rats were intravenously administered gadotamide meglumine at doses of 0, 2, 4, and 10 mmol/kg/day (or, based on body surface area, equivalent to 3.2, 6.5, and 16.2 times the recommended human dose) throughout the mating period up to day 17 of gestation (GD17), 14 days prior to mating. In pregnant rabbits, gadotamide was administered intravenously from day 6 (GD6) to day 19 (GD19) at doses of 0, 1, 3, and 7 mmol/kg/day (or, on a body surface area basis, equivalent to 3.3, 10, and 23 times the human dose, respectively). No effects on embryonic development were observed at doses up to 10 mmol/kg/day in rats and up to 3 mmol/kg/day in rabbits. Maternal toxicity was observed at a dose of 10 mmol/kg/day in rats (or 16 times the human dose on a body surface area basis) and at a dose of 7 mmol/kg/day in rabbits (23 times the human dose on a body surface area basis).
Special Risk Populations
In the clinical studies of DOTAREM, 900 patients were 65 years of age or older, and 312 patients were 75 years of age or older. No overall differences in safety and efficacy were observed between these subjects and younger subjects. Generally, caution should be exercised when using DOTAREM in elderly patients, as impaired renal function and comorbidities or concurrent drug treatments are more common in this age group. No age-based dose adjustment is necessary.
Gadolinium-based contrast agents (GBCAs) increase the risk of renal systemic fibrosis (NSF) in patients with impaired drug clearance. GBCAs should be avoided in these patients unless diagnostic information is critical and unavailable through non-contrast MRI or other diagnostic methods. Renal systemic fibrosis (NSF) can lead to fatal or disabling fibrosis affecting the skin, muscles, and internal organs. The risk of NSF is highest in patients with chronic severe kidney disease (glomerular filtration rate (GFR) < 30 mL/min/1.73 m²) or acute kidney injury. Patients should be screened for acute kidney injury and other conditions that may impair renal function. For patients at risk of chronic renal decline (e.g., age > 60 years, hypertension, diabetes), GFR should be estimated by laboratory tests. For patients at high risk of renal systemic fibrosis (NSF), do not exceed the recommended dose of DOTAREM and allow sufficient time for the drug to be cleared from the body before re-administering.

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Target: Gadolinium complexes are not considered a high-risk class of drugs for prolonging cardiac repolarization (which may lead to potentially life-threatening arrhythmias such as torsades de pointes). However, although these compounds are widely used as contrast enhancers in magnetic resonance imaging, reliable data on them remain limited. This article summarizes recently obtained cardiovascular safety data for gadoteryl meglumine (Gd-DOTA).
Materials and Methods: The cardiovascular safety of Gd-DOTA was evaluated using state-of-the-art nonclinical in vitro (canine Purkinje fibers) and in vivo research methods. In vivo studies included normal animal models (dogs) and sensitized animal models (rabbits), as well as patients with various diseases in a specific clinical trial.
Results: In all these studies, Gd-DOTA did not show any direct harmful effects on cardiac electrophysiology, particularly ventricular repolarization. Conclusion: These results confirm the good safety profile of Gd-DOTA as determined by post-marketing assessment. The nonspecific gadolinium complex used for magnetic resonance contrast enhancement does not fall into the risk category of drug-related arrhythmias. [1]

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The toxicity profile of gadoterate meglumine is generally favorable due to its high stability and low release of free Gd³⁺. Common adverse effects include nausea, headache, and injection site reactions. Serious adverse reactions are rare. The macrocyclic structure provides a more favorable safety profile compared to linear GBCAs. Contraindications include hypersensitivity to gadolinium-based contrast agents. The risk of nephrogenic systemic fibrosis is very low with macrocyclic agents like gadoterate meglumine.

[1]. Cardiovascular safety of gadoterate meglumine (Gd-DOTA). Investigative radiology, 2007, 42(2): 63-77.

Drug Warning
/Black Box Warning/ Warning: Gadolinium-based contrast agents (GBCAs) increase the risk of NSF in patients with impaired drug clearance. GBCAs should be avoided in these patients unless diagnostic information is critical and cannot be obtained via non-contrast MRI or other examinations. NSF can lead to fatal or disabling fibrosis affecting the skin, muscles, and internal organs. The following patients are at highest risk of developing NSF: chronic severe kidney disease (glomerular filtration rate (GFR) < 30 mL/min/1.73 m2) or acute kidney injury. Patients should be screened for acute kidney injury and other conditions that may impair kidney function. For patients at risk of chronic kidney decline (e.g., age > 60 years, hypertension, diabetes), glomerular filtration rate (GFR) should be estimated by laboratory tests. For patients at high risk of NSF, do not exceed the recommended DOTAREM dose and allow sufficient time for drug clearance before re-administering.
In patients with chronic renal impairment, the use of gadolinium-based contrast agents (GBCAs) may lead to acute kidney injury requiring dialysis. The risk of acute kidney injury may increase with increasing contrast agent dose; the lowest dose required to achieve adequate imaging should be used. Screen all patients for renal impairment by taking their medical history and/or performing laboratory tests. Follow-up renal function assessments should be considered for patients with a history of renal impairment.
Before administering DOTAREM, ensure the catheter and vein are patent. Leakage into tissues during DOTAREM administration may cause tissue irritation.
Visually inspect the DOTAREM solution for particulate matter before administration. Do not use the solution if particulate matter is present or the container is broken. DOTAREM should be a clear, colorless to pale yellow solution. Do not mix with other medications or parenteral nutrition solutions. Discard any unused portions of the medication.
Maximum Dosage
Tolerance of DOTAREM at cumulative doses up to 0.3 mmol/kg in healthy volunteers and patients is similar to that at lower doses.

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This compound is the meglumine salt of gadoteric acid. It is marketed under various brand names for MRI contrast enhancement. The molecular formula is C₁₆H₂₅GdN₄NaO₈·C₇H₁₇NO₅, and the molecular weight is approximately 753.9 g/mol. It is a clear, colorless to slightly yellow solution for intravenous injection. This product has received regulatory approval in many countries including the US FDA and EMA for use in MRI of the central nervous system and other body regions. It is not a drug in the traditional sense but a diagnostic imaging agent.

C23H42GDN5O13

753.86

754.202

92943-93-6

72573-82-1

6918037

White to off-white solid powder

7

18

11

42

644

4

CNC[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.C1CN(CCN(CCN(CCN1CC(=O)O)CC(=O)[O-])CC(=O)[O-])CC(=O)[O-].[Gd+3]

RYHQMKVRYNEBNJ-BMWGJIJESA-K

InChI=1S/C16H28N4O8.C7H17NO5.Gd/c21-13(22)9-17-1-2-18(10-14(23)24)5-6-20(12-16(27)28)8-7-19(4-3-17)11-15(25)26;1-8-2-4(10)6(12)7(13)5(11)3-9;/h1-12H2,(H,21,22)(H,23,24)(H,25,26)(H,27,28);4-13H,2-3H2,1H3;/q;;+3/p-3/t;4-,5+,6+,7+;/m.0./s1

2-[4,7-bis(carboxylatomethyl)-10-(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate;gadolinium(3+);(2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol

Dotaline; Gd-DOTA; Magnescope; P-449

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)