Dihydroergotamine Impurities and Dihydroergotamine
Daicel Pharma synthesizes high-quality impurities for Dihydroergotamine, an active pharmaceutical ingredient. These impurities, including Dihydroergotamine impurity D and Dihydrolysergamide, help in assessing Dihydroergotamine purity, reliability, and safety. Daicel Pharma also offers a customized synthesis of Dihydroergotamine impurities to cater to client requirements, with worldwide delivery options available.
Dihydroergotamine [CAS: 511-12-6] is a derivative of ergotamine that treats migraine headaches. It is a vasoconstrictor for the management of migraine disorders. It acts as a serotonergic agonist, a non-narcotic analgesic, a vasoconstrictor agent, a dopamine agonist, and a sympatholytic agent.
Dihydroergotamine: Use and Commercial Availability
Dihydroergotamine (DHE) treats migraine, even during the prevalence of triptans. It interacts with 5-HT1A and 5-HT2 receptors and alpha-1 and -2 receptors, indicating its potential to provide therapeutic benefits through multiple receptor mechanisms. Dihydroergotamine is available in nasal spray and injectable forms (IV, IM, or SC). Clinical trials of orally inhaled DHE have demonstrated its effectiveness in relieving headaches and associated symptoms like nausea, photophobia, and phonophobia. D.H.E. 45, Dihydroergotamine Mesylate, Embolex, Migranal, and Trudhesa are some of the brand names under which the drug is available.
Dihydroergotamine Structure and Mechanism of Action
The chemical name of Dihydroergotamine is (5′α,10α)-9,10-Dihydro-12′-hydroxy-2′-methyl-5′-(phenylmethyl)ergotaman-3′,6′,18-trione. Its chemical formula is C33H37N5O5, and its molecular weight is approximately 583.7 g/mol.
Dihydroergotamine binds with 5-HT1Dα and 5-HT1Dβ receptors. It acts as a selective agonist for the 5-HT1B/D receptors, leading to cranial vasoconstriction and inhibition of calcitonin gene-related peptide (CGRP) release from trigeminal afferents during migraine episodes. It possesses oxytocic properties.
Dihydroergotamine Impurities and Synthesis
Dihydroergotamine impurities can originate from various sources, including the synthetic process1, degradation over time, or impure starting materials. They affect the drug quality, efficacy, and safety. The analysis and control of these impurities are crucial to ensure the purity and reliability of the final product. They can impact the drug’s stability, pharmacokinetics, and potential adverse effects. Therefore, comprehensive analysis and control of Dihydroergotamine impurities are necessary to comply with regulatory guidelines and ensure patient safety. It involves thorough characterization, quantification, and implementing measures to minimize impurity formation during manufacturing and storage.
Daicel Pharma offers a comprehensive Certificate of Analysis (CoA) for Dihydroergotamine impurity standards, including Dihydroergotamine impurity D and Dihydrolysergamide. They generate from an analytical facility that complies with cGMP standards. The CoA provides a detailed characterization report with data obtained through techniques such as 1H NMR, 13C NMR, IR, MASS, and HPLC purity analysis2. We give additional data like 13C-DEPT upon request. Daicel Pharma synthesizes unknown Dihydroergotamine impurities or degradation products, and labeled compounds, to evaluate the efficacy of generic Dihydroergotamine. Also, Dihydroergotamine D3, a deuterium-labeled Dihydroergotamine standard, is available for bio-analytical research, including BA/BE studies. Every delivery accompanies a complete characterization report.
- Stoll, Arthur; Hofmann, Albert, Methane Sulfonic Acid Salt Of Di-Hydro-Ergotamine, Sandoz Ltd., US2507830A, May 16, 1980
- Niazy, Esmail M.; Molokhia, Abdulla M.; El-Gorashi, Abubakr S., Quick and simple determination of dihydroergotamine by high-performance liquid chromatography, Analytical Letters, Volume: 21, Issue: 10, Pages: 1833-43, 1988
Frequently Asked Questions
The potential sources of Dihydroergotamine impurities during synthesis include contaminants in raw materials, incomplete reaction conversions, side reactions, and residual solvents or reagents.
Dihydroergotamine impurities are regularly monitored post-manufacturing to assess the stability and quality of the drug product over its shelf life. Monitoring frequency may vary depending on regulatory requirements and the specific formulation of the drug.
To minimize the formation of Dihydroergotamine impurities, manufacturers can ensure the use of high-quality starting materials, optimize reaction conditions, implement effective purification techniques, and maintain proper storage and handling conditions.
It may not be possible to eliminate impurities. Their levels can be controlled and minimized through optimized manufacturing processes, appropriate storage conditions, and strict quality control measures.
Dihydroergotamine impurities are stored at a controlled room temperature between 2-8 °C or as indicated on the Certificate of Analysis (CoA).
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