Determination of methylprednisolone metabolites in human urine by gas chromatography-mass spectrometry

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

doi:10.1016/0378-4347(87)80323-7

Cited by 30 publications

(23 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The GC/MS spectrum for the MO‐TMS derivative of M1 showed a molecular ion at m/z 574, characteristic fragment ions formed by loss of the oxime and O‐TMS groups at m/z 543, 453, 484 and 453 (Table ) and ions at m/z 202, and 229 arising from C ring fragmentations. This is in agreement with published data …”

Section: Results and Discusionsupporting

confidence: 94%

Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine

Pozo

Marcos

Matabosch

et al. 2012

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

show abstract

Section: Results and Discusionsupporting

confidence: 94%

Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine

Pozo

Marcos

Matabosch

et al. 2012

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

show abstract

“…Methylprednisolone undergoes a variety of biotransformation processes that involve the mixed-function oxidase system of the liver and possibly other organs, including CYP3A-catalyzed 6β-hydroxylation. 27,28 Thus the findings of Hunt et al 26 concur with our observation of faster clearance of methylprednisolone in women. This produces a shorter elimination half-life in women and is an important feature because the latter determines how long plasma methylprednisolone concentrations exceed the IC 50 value and thus how long suppressive responses will be maintained.…”

Section: Discussion Pharmacokineticssupporting

confidence: 88%

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

Lew

Ludwig

Milad

et al. 1993

Clin Pharmacol Ther

155

View full text Add to dashboard Cite

The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC 50 ) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC 50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response.Male subjects typically have been used in most drug studies. However, the findings of these studies are applied clinically to both male and female patients, despite their physiologic differences. Of the studies that have enrolled both men and women, most fail to analyze their findings by gender and instead treat all the subjects as one homogeneous group. 1 This bias in clinical research has been of concern within the health professions. [2][3][4] The literature currently lacks guidelines regarding dosing regimens based on gender.Copyright © 1993 by Mosby-Year Book, Inc.Reprint requests: William J. Jusko, PhD, Hochstetter 565, School of Pharmacy, State University or New York at Buffalo, Buffalo, NY 14260. Presented at the Ninety-fourth Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, March 24-26, 1993, Honolulu, Hawaii (Abstract: Clin Pharmacol Ther 1993;53:183). NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2014 October 23. Published in final edited form as:Clin Pharmacol Ther. 1993 October ; 54(4): 402-414. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptGender-related differences in disposition have been observed for numerous drugs. The total and unbound clearance of diazepam, which undergoes oxidative metabolism, was found to be greater in women. 5 Clearance of oxazepam (total and unbound) 6 and acetaminophen, 7 both of which undergo glucuronide conjugation, is significantly greater ...

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

Determination of methylprednisolone metabolites in human urine by gas chromatography-mass spectrometry

Cited by 30 publications

References 8 publications

Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine

Using complementary mass spectrometric approaches for the determination of methylprednisolone metabolites in human urine

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

Identification of budesonide metabolites in human urine after oral administration

Contact Info

Product

Resources

About