Gas chromatographic and mass spectral study of betamethasone synthetic corticosteroid metabolism

Rodchenkov, G. M.; Uralets, V. P.; Semenov, V. A.; Gurevich, V. A.

doi:10.1016/s0378-4347(00)80654-4

Cited by 13 publications

(12 citation statements)

References 11 publications

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“…Former studies in glucocorticosteroids metabolism were performed using gas chromatography coupled to mass spectrometry (GC/MS) [14][15][16][17]. In the last years, the use of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has demonstrated to be useful for the identification of new metabolites of steroids, including glucocorticosteroids [18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Identification of budesonide metabolites in human urine after oral administration

Matabosch¹,

Pozo²,

Pérez‐Mañá

et al. 2012

Anal Bioanal Chem

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Budesonide (BUD) is a glucocorticoid widely used for the treatment of asthma, rhinitis, and inflammatory bowel disease. Its use in sport competitions is prohibited when administered by oral, intravenous, intramuscular, or rectal routes. However, topical preparations are not prohibited. Strategies to discriminate between legal and forbidden administrations have to be developed by doping control laboratories. For this reason, metabolism of BUD has been re-evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with different scan methods. Urine samples obtained after oral administration of 3 mg of BUD to two healthy volunteers have been analyzed for metabolite detection in free and glucuronide metabolic fractions. Structures of the metabolites have been studied by LC-MS/MS using collision induced dissociation and gas chromatography-mass spectrometry (GC/MS) in full scan mode with electron ionization. Combination of all structural information allowed the proposition of the most comprehensive picture for BUD metabolism in humans to this date. Overall, 16 metabolites including ten previously unreported compounds have been detected. The main metabolite is 16α-hydroxy-prednisolone resulting from the cleavage of the acetal group. Other metabolites without the acetal group have been identified such as those resulting from reduction of C20 carbonyl group, oxidation of the C11 hydroxyl group and reduction of the A ring. Metabolites maintaining the acetal group have also been identified, resulting from 6-hydroxylation (6α and 6β-hydroxy-budesonide), 23-hydroxylation, reduction of C6-C7, oxidation of the C11 hydroxyl group, and reduction of the C20 carbonyl group. Metabolites were mainly excreted in the free fraction. All of them were excreted in urine during the first 24 h after administration, and seven of them were still detected up to 48 h after administration for both volunteers.

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Section: Introductionmentioning

confidence: 99%

Identification of budesonide metabolites in human urine after oral administration

Matabosch¹,

Pozo²,

Pérez‐Mañá

et al. 2012

Anal Bioanal Chem

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“…Betamethasone's main excretionary products in horses are betamethasone and 6-hydroxy betamethasone (Rodchenkov, 1988). Methylprednisolone's main metabolites are methylprednisone, 20-dihydromethylprednisolone, 20-dihydromethylprednisone Stenhouse, 1990), 17,21-dihydroxy-6alpha-methyl-1,4 pregnadiene-3,11,20-trione, 6alfa-methyl-17,20 beta,21-trihydroxy-1-4 pregnadiene-3,11 dione and6 alpha -methyl11b,17,20 beta,21-tetrahydroxy-1,4 pregnadien-3-one (Gallciano et al,1985).…”

Section: Figure 2 Route From Cholesterol To Cortisol (Garrett and Grmentioning

confidence: 99%

“…This situation is complicated further because levels of these substances can increase up to 50% in response to exercise (McKenna, 1994). (Rodchenkov, 1988, Skrabalak, 1982 Exercise and breed of horse affect glucocorticoid levels. A study of trotting horses and standardbred horses gave an arithmetic mean post race cortisol level in serum of 71 ng/ml with a range of 39-141 ng/ml.…”

Section: Factors Affecting Glucocorticoid Concentrationmentioning

confidence: 99%

“…Another experiment demonstrated varying amount of derivatized fractions depending upon temperature used in the derivatization process (Rodchenkov, 1988). For betamethasone, a derivitisation temperature of 80 0 C for 3 hours yielded a mono-methoxyamine (MO) derivative.…”

Section: Chemical Analysismentioning

confidence: 99%

“…This experiment also demonstrated that betamethasone required a more rigorous derivatization procedure than dexamethasone required. (Rodchenkov, 1988). Schnazner (1994) stated that steric hindrance created by the 9-fluoro group retards derivitization of the 11-beta hydroxyl group.…”

Section: Chemical Analysismentioning

confidence: 99%

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A new robust technique for testing of glucocorticosteroids in dogs and horses

Webster

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Detection and characterization of betamethasone metabolites in human urine by LC‐MS/MS

Matabosch

Pozo

Monfort

et al. 2014

Drug Testing and Analysis

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Glucocorticosteroids are prohibited in sports when administered by systemic routes and allowed using other administrations for therapeutic reasons. Therefore, markers to distinguish between routes of administration through the analysis of urine samples are needed in anti-doping control. As a first step to achieve that goal, the metabolism of betamethasone (BET) was investigated in the present work. Urine samples obtained after BET intramuscular injection were hydrolyzed with β-glucuronidase and subjected to liquid-liquid extraction with ethyl acetate in alkaline conditions. The extracts were analyzed by liquid chromatography coupled to tandem mass spectrometry. Common open screening methods for fluorine containing corticosteroids (precursor ion scan method of m/z 121, 147, 171, and neutral loss (NL) scan methods of 20 and 38 Da in positive ionization, and 46 and 76 Da in negative ionization) were applied to detect BET metabolites. Moreover, an NL method was applied to detect A-ring reduced metabolites of BET, which are ionized as [M+NH4 ](+) (NL of 55, 73, and 91 Da, corresponding to the consecutive losses of NH3 , HF and one, two and three water molecules, respectively). BET and 24 metabolites were detected. Six metabolites were identified by comparison with standards, and for ten, feasible structures were proposed based on mass spectrometric data. Eleven of the characterized metabolites had not been previously reported. Metabolites resulting from 11-oxidation, 6-hydroxylation, C20 or 4-ene-3-one reduction and combination of some of them were detected. Moreover one metabolite resulting from cleavage of the side chain with subsequent oxidation of carbon at C17 was also detected.

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Gas chromatographic and mass spectral study of betamethasone synthetic corticosteroid metabolism

Cited by 13 publications

References 11 publications

Identification of budesonide metabolites in human urine after oral administration

Identification of budesonide metabolites in human urine after oral administration

A new robust technique for testing of glucocorticosteroids in dogs and horses

Detection and characterization of betamethasone metabolites in human urine by LC‐MS/MS

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