Dexamethasone: A Brief Analysis

Dexamethasone is a glucocorticoid (a class of corticosteroid) and is used for the treatment of various anti-inflammatory conditions which includes rheumatic disorders and bronchial asthma and autoimmune conditions. Patients suffering from cancer and undergoing chemotherapy are also sometimes given Dexamethasone to prevent the side effects of the antitumor treatments.

Dexamethasone medication is also recommended for?

Dexamethasone was recommended for use in COVID -19 for patients with severe respiratory symptoms. Dexamethasone was recommended in the UK by National Health Service and also in the US by the National Institute of Health (NIH) for patients with COVID-19 who need supplement Oxygen or mechanical ventilation.

Dexamethasone is also used in the treatment of high-altitude cerebral edema (HACE) and also as high-altitude pulmonary edema (HAPE). It is often carried during mountain climbing expeditions which helps the climbers with complications of altitude sickness.

Dexamethasone has veterinary applications when combined with marbofloxacin and clotrimazole and is also available as Aurizon for treatment in dogs for the treatment of difficult ear infections.      

Dexamethasone was synthesized first in the year 1957 and FDA granted the approval for medical use in 1958, it is in the World Health Organization’s list of Essential Medicines.    

Dexamethasone an overview:

Dexamethasone is available as generic and as brands Baycadron, Ciprodex, Dextenza, Dioptrol, etc. The drug is available in most parts of the world. Dexamethasone is a synthetic pregnane corticosteroid and is the derivative of cortisol and its X-ray crystallography has determined its molecular and crystal structure. Dexamethasone comes in the form of tablets, injections, topical creams,s or ointments,s and also for the eyes as a topical ophthalmic solution and ear drops. 

In the year 1958, Taub did the synthesis of beta-substituted cortical steroid derivatives, and 16 beta-methylprednisolone acetates were obtained, further 16 beta-methylprednisolone acetate is dehydrated to 9,11 dihydro derivative which was converted to 9 alpha bromo-11 beta hydrin derivative which determines the epoxide ring closure, Dexamethasone formation takes place by the ring opening reaction with hydrogen fluoride in THF.

Further continual process improvement in the synthesis of Dexamethasone, Research, and development has taken place which leads to feasible process at a commercial level, to control the impurities as per the regulatory guidelines ICH (International Conference on Harmonization), yield improvement and various methods are available for synthesis as reported in the literature.

The structure of Dexamethasone is represented as:

DEXAMETHASONE A BRIEF ANALYSIS

CAS No. 50-02-2

Molecular Formula: C22H29FO5

Molecular Weight: 392.46

IUPAC Name: (11β,16α)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione

Overall the period the manufacturing process of the active substance ingredient (API) is developed with an improved, robust, and most importantly to develop economically viable process at all the stages including the intermediates to control the impurities. Further, the starting material is to be chosen correctly, its availability and its cost are also considered.

The process and the impurities are always considered critical as it depends on the manufacturing process and its process parameters. There are various analytical techniques that are used and can control and detect the impurities at different stages during the manufacturing process. They can be analyzed and characterized by using mass, IR, NMR spectroscopy, and HPLC column chromatography to get the product purity as per pharmacopeia. The specification and the critical intermediates have limits for the specified and unspecified impurities and also the impurity profile for the final active pharmaceutical ingredient (API).

 Which are the Impurities reported for Dexamethasone?

Several impurities of Dexamethasone have been isolated and purified by chemical synthetic methods and analytical techniques and are reported in pharmacopeia and also Dexamethasone is available at Veeprho as EP Pharmacopeial and non-pharmacopeial impurities.

LIST OF DEXAMETHASONE IMPURITIES:

Catalogue No.Dexamethasone ImpuritiesCAS No.
VL273023Dexamethasone EP Impurity AN/A
VL273010Dexamethasone EP Impurity B378-44-9
VL273017Dexamethasone EP Impurity C426-17-5
VL273018Dexamethasone EP impurity D24916-90-3
VL273016Dexamethasone EP Impurity E13209-41-1
VL273011Dexamethasone EP Impurity F382-67-2
VL273012Dexamethasone EP Impurity G1177-87-3
VL273024Dexamethasone EP Impurity H10106-41-9
VL273006Dexamethasone EP Impurity I14622-47-0
VE006073Dexamethasone EP Impurity J2036-77-3
VL273007Dexamethasone EP Impurity K1809224-82-5
VL273021Dexamethasone Acetate EP Impurity A50-02-2
VL273019Dexamethasone Acetate EP Impurity CN/A
VL273022Dexamethasone Acetate EP Impurity D987-24-6
VE005876Dexamethasone Acetate EP Impurity E1524-94-3
VE008475Dexamethasone Acetate EP Impurity F2884-51-7
VE008476Dexamethasone Acetate EP Impurity G1597-78-0
VE005877Dexamethasone Acetate EP Impurity I3949-26-6
VE006236Dexamethasone sodium phosphate EP Impurity B151-73-5
VE006237Dexamethasone sodium phosphate EP Impurity CN/A
VE006238Dexamethasone Sodium Phosphate EP Impurity DN/A
VE006239Dexamethasone sodium phosphate EP Impurity EN/A
VE006240Dexamethasone Sodium Phosphate EP Impurity FN/A
VE005886Dexamethasone Sodium Phosphate EP impurity G37927-01-8
VE006241Dexamethasone Sodium Phosphate EP Impurity H162968-22-1
VE006242Dexamethasone Sodium Phosphate DiesterN/A
VE005952Dexamethasone Impurity 41188271-71-7
VE005888Dexamethasone Impurity 7N/A
VE0010105Dexamethasone Impurity 13N/A
VE009870Dexamethasone Impurity 14N/A
VE009872Dexamethasone Impurity 15N/A
VE009873Dexamethasone Impurity 16N/A
VE005953Dexamethasone Acid 17-O-Formyl Impurity473273-04-0
VE006401Dexamethasone Desfluoro 11-Epimer78761-59-8
VE006194Dexamethasone ethyl ester ImpurityN/A
VE009290Dexamethasone Glyoxal Analog84449-15-0
VL273003Dexamethasone-Δ 17 | 20 21-Aldehyde6762-51-2
VE005887Dexamethasone 17-Ketone2285-53-2
VE007346Dexamethasone 17-Propionate15423-89-9
VL27300417 Desoxy of DexamethasoneN/A
VE00941817-dexamethasone sodium phosphateN/A
VL27300117-Oxo Dexamethasone1880-61-1
VL27300217β-Carboxy-17-Desoxy Dexamethasone75262-69-0
VL27300821 Dehydro Dexamethasone2964-79-6
VE00939221-​Hemiacetal Dexamethasone473273-03-9
VE00939321-Chloro DexamethasoneN/A
VE00874621-Dehydro Dexamethasone Hydrate2964-79-6
VL27302021-dehydro-17-deoxy dexamethasoneN/A
VE00941921-dihydrodexamethasoneN/A
VE00939121-Methyl DexamethasoneN/A
VE0060926-alfa Hydroxy Dexamethasone111897-35-9
VE0060916-beta Hydroxy Dexamethasone55879-47-5
VL2730059-Desfluoro-11-Keto DexamethasoneN/A
VE008749delta9 (11)-21- Ethyl formate Dexamethasone89561-92-2
VE008747(11β | 16α)-9-Bromo-21-[(ethoxycarbonyl)oxy]-11-(formyloxy)-
17-hydroxy-16-methylpregna-1 | 4-diene-3 | 20-dione
192447-02-2

Dexamethasone is used for the treatment of various anti-inflammatory conditions which includes rheumatic disorders, bronchial asthma, and autoimmune conditions. Dexamethasone is available as a generic drug and in different brands. The drug is available in most parts of the world. Dexamethasone comes in the form of tablets, injections, topical creams or ointments, and also for the eyes as a topical ophthalmic solution, and ear drops. 

References:

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