Gadopentetate Dimeglumine

Product Overview

Gadopentetate dimeglumine (Gd-DTPA dimeglumine) is the first intravenous gadolinium-based MRI contrast agent to enter clinical use, marketed as Magnevist, developed by Bayer, with ATC code V08CA01. Although a large number of structurally similar gadolinium chelates (GBCAs) have since been introduced, gadopentetate dimeglumine remains the prototype and reference standard of the “conventional extracellular space contrast agents”.

Chemical composition: Diethylenetriaminepentaacetic acid (DTPA, pentetic acid) is chelated with trivalent gadolinium ion (Gd³⁺) to form gadopentetic acid (C₁₄H₂₀GdN₃O₁₀), which is then salified with 2 molecules of meglumine (1-deoxy-1-(methylamino)-D-glucitol) — hence the name “dimeglumine”. As the counterion, meglumine not only improves water solubility but also contributes to formulation osmolality and tolerability.

Mechanism of action: Gd³⁺ is a lanthanide ion with 7 unpaired electrons; when placed in a magnetic field it generates a large magnetic moment that shortens the T1 and T2 relaxation times of surrounding water protons. At conventional clinical doses, the T1 effect predominates, manifesting as increased tissue signal (brightening) on T1-weighted sequences.

In vivo distribution characteristics (the origin of “extracellular space contrast agent”): The molecule is highly hydrophilic, binds plasma proteins almost negligibly, and is biologically inert. After intravenous injection it rapidly distributes into the extracellular fluid (intravascular + interstitial space), does not enter cells, and does not cross the intact blood-brain barrier — for this reason it can enhance three categories of structures: CNS tissues lacking a blood-brain barrier (e.g., the pituitary), extra-axial tumors (e.g., meningiomas), and regions of blood-brain barrier disruption (e.g., tumor margins, inflammatory/demyelinating lesions). This is also its most fundamental difference from gadoxetate disodium (which is taken up by hepatocytes): it has no organ or cell targeting and distributes non-specifically.

Excretion: Excreted unchanged by glomerular filtration; clearance is rapid in patients with normal renal function.

Formulation essentials: Each mL contains 469.01 mg of gadopentetate dimeglumine (equivalent to 0.5 mmol/mL), plus small amounts of free meglumine (0.99 mg) and pentetic acid (DTPA, 0.40 mg) — the latter serving as a chelating agent to complex any free gadolinium that may dissociate and reduce toxicity, a classic design feature of this class of formulations.

Technical Specifications

• Standards: CHP/USP/EP
• Specification: 0.99 (purity ≥99.0%); the ChP formulation monograph requires the content of gadopentetate dimeglumine (C₁₄H₂₀GdN₃O₁₀·2C₇H₁₇NO₅) to be 95.0%–105.0% of the labeled amount
• CAS No.: 86050-77-3 (gadopentetate dimeglumine, EINECS 1308068-62-2, UNII 8118U4V3H6, ATC V08CA01, MDL MFCD00867271); the corresponding gadopentetic acid (free chelated acid) is 80529-93-7
• Molecular formula: C₁₄H₂₀GdN₃O₁₀·2C₇H₁₇NO₅ (used by ChP and all package inserts); combined formula written as C₂₈H₅₄GdN₅O₂₀
• Molecular weight: 938.01 (ChP 2025, Chinese package inserts); the Magnevist product monograph reports 938.02; suppliers generally report 938.00; free gadopentetic acid C₁₄H₂₀GdN₃O₁₀ is 547.58
• Appearance: White or off-white crystalline powder; odorless, slightly sweet taste (ChP and Chinese sources); suppliers generally describe it as a white to off-white/beige solid
• Purity (HPLC): ≥ 99.0%
• Melting point: No official melting point has been found in ChP/USP/EP or in published FDA/EMA documentation. As an ionic metal chelate salt, it typically decomposes at elevated temperature rather than melting; industry practice is to substitute melting-point testing with thermogravimetric analysis (TGA) / differential scanning calorimetry (DSC) together with controls for moisture, gadolinium content and related substances. Note: an individual supplier was found to report “220 °C (decomposition)”, and a literature value of 129 °C (decomposition) exists for gadopentetic acid (the free acid, 80529-93-7) — these are different substances, and neither is a pharmacopoeial value; if this field is mandatory on the site, we recommend entering “not applicable” or “per measured TGA/DSC” and do not recommend directly citing supplier values
• Specific optical rotation: Not found in pharmacopoeias or authoritative standards; the molecule contains the chiral centers of meglumine (2R,3R,4R,5S); quality control is typically achieved through gadolinium content, related substances, pH and osmolality instead
• Chemical name: Dihydrogen [N,N-bis[2-[bis(carboxymethyl)amino]ethyl]glycinato(5-)]gadolinium(2-) compound with 1-deoxy-1-(methylamino)-D-glucitol (1:2); in short, diethylenetriaminepentaacetic acid gadolinium dimeglumine
• Solubility: Freely soluble in water (ChP and Chinese sources; the Magnevist monograph states “freely soluble in water”); reagent grade: DMSO approximately 100 mg/mL (with sonication), water approximately 10 mg/mL (with sonication — not contradictory to actual solubility at formulation concentration, since the formulation is a high-concentration aqueous system of 469 mg/mL)
• Gadolinium content: Approximately 16.76% (theoretical approximately 16.7%)
• Formulation physicochemical parameters (0.5 mmol/mL injection): Contrast agent concentration 469.01 mg/mL; osmolality at 37 °C approximately 1960 mOsm/kg H₂O (1.96 Osm/kg); viscosity 2.9 mPa·s (37 °C) / 4.9 mPa·s (20 °C); density 1.195 g/mL (37 °C) / 1.210 g/mL (20 °C); pH 7.0–7.9
• Computed physicochemical parameters: LogP approximately −12.6; topological polar surface area approximately 431 Ų
• Storage conditions: Protected from light, sealed, under inert gas, at room temperature or 2–8 °C, dry (supplier recommendations vary); injection stored at 15–30 °C, protected from light (Magnevist monograph); do not freeze

Applications

• Central nervous system MRI (core indication): MRI of the brain and spinal cord. Particularly suited for confirming tumors and for further differential diagnosis of suspected meningiomas, (acoustic) schwannomas, infiltrative tumors (e.g., gliomas) and metastases; confirming small tumors and/or isointense tumors; suspected tumor recurrence after surgery or radiotherapy; differentiating rare tumors such as hemangioblastomas, ependymomas and small pituitary adenomas; and determining the extent of spread of non-brain-derived tumors. In spinal cord imaging it is also used to differentiate intramedullary from extramedullary tumors, to demonstrate solid tumor areas in known fistulas, and to determine the spread of intramedullary tumors
• Whole-body MRI: Magnetic resonance imaging of body organs and tissues including the abdomen, thorax, pelvis and extremities. Blood vessels, organs and non-bony tissues outside the central nervous system are displayed more clearly after enhancement. Optimal enhancement generally occurs within 45 minutes of injection; for cranial examinations optimal enhancement usually occurs within 27 minutes of injection, and for spinal cord examinations in the early post-administration period (10–30 minutes); in neonates and infants, optimal enhancement of the central nervous system can persist for several hours
• Dosage and administration: For intravenous injection only. Adults and children over 2 years: 0.2 mL/kg body weight (or 0.1 mmol/kg), maximum dose 0.4 mL/kg. For cranial and spinal cord MRI, a repeat dose may be given within 30 minutes if necessary; for whole-body MRI, 0.4 mL/kg may be administered to obtain adequate enhancement; to exclude lesions or tumor recurrence in adults, the dose may be increased to 0.6 mL/kg to improve diagnostic confidence. The lowest approved dose should be used whenever possible, and imaging should be completed within 1 hour of administration
• Pharmacology and mechanism research: For T1/T2 relaxivity measurement, evaluation of gadolinium chelate stability and free gadolinium release, blood-brain barrier integrity assessment, extracellular space distribution and glomerular filtration studies, and as a reference comparator for novel contrast agents
• Formulation and manufacturing: For formulation development of the injection (0.5 mmol/mL; presentations 10 mL:4.69 g, 12 mL:5.63 g, 15 mL:7.04 g, 20 mL:9.38 g, calculated as C₁₄H₂₀GdN₃O₁₀·2C₇H₁₇NO₅); excipients include meglumine, pentetic acid (DTPA, chelating agent) and water for injection. Key manufacturing control points include gadolinium content and complexation stability, free Gd³⁺, related substances, pH (7.0–7.9) and high osmolality (approximately 1960 mOsm/kg — markedly higher than plasma and one of the causes of its injection-site reaction and tolerability profile); suitable for analytical method development and validation, stability studies, and GMP scale-up and CMO/CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended solely for legitimate industrial, research and pharmaceutical manufacturing use, and does not constitute end-user clinical or self-administration guidance. The finished product is a prescription drug and must be used by specialist radiologists in settings equipped with resuscitation equipment and personnel, and in compliance with standard MRI safety regulations (contraindicated in patients with cardiac pacemakers or ferromagnetic implants). Warnings for gadolinium-based contrast agents (GBCA): ① Use of GBCAs in patients with severe renal impairment may increase the risk of nephrogenic systemic fibrosis (NSF); ② This product is a linear GBCA — both linear and macrocyclic GBCAs cause trace gadolinium deposition in the brain and other tissues, and animal studies show greater deposition with linear agents than with macrocyclic agents after repeated use; the lowest approved dose should therefore be used whenever possible and unnecessary repeat contrast-enhanced examinations should be avoided. Hypersensitivity reactions have been reported. Common adverse reactions in clinical studies include nausea, headache, dizziness, injection-site reactions (pain, burning, coldness, extravasation, irritation), dysgeusia, flushing, vomiting and elevated blood pressure, mostly mild to moderate. When handling the API, wear protective gloves, protective clothing and eye/face protection, and avoid dust inhalation.

Product information: please contact us. This information is for reference only.