Complementary use of ion trap/time-of-flight mass spectrometry in combination with capillary high-pressure liquid chromatography: early characterization of in vivo metabolites of the cathepsin K inhibitor NVP-AAV490 in rat

Blum, W.; Buhl, Thomas; Altmann, Eva; Kühnöl, Jürgen; Ramstein, Philippe; Aichholz, Reiner

doi:10.1016/s1570-0232(02)00782-1

Cited by 3 publications

(1 citation statement)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, this method has infrequently been applied for characterization of metabolites° [25][26][27][28][29][30][31][32][33].°The°higher°cost°of°D 2 O could be considered a certain drawback, but the consumption of D 2 O can be significantly reduced by using smaller columns and smaller solvent bottles. Alternatively, fractions can be collected and redissolved in D 2 O containing solvents.…”

Section: H/d Exchangementioning

confidence: 99%

Structural characterization of sulfadiazine metabolites using H/D exchange combined with various MS/MS experiments

Pfeifer¹,

Tuerk

Fuchs³

2005

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Two major metabolites and one minor metabolite of sulfadiazine were found in pig manure, using a special combination of different MS techniques like parent and product ion scans, H/D exchange, accurate mass measurement, and MS/MS experiments with substructures. N4-acetylsulfadiazine and 4-hydroxysulfadiazine were identified as major metabolites. N4-acetylsulfadiazine could be verified by H/D exchange and comparison with product ion spectra of a synthetic reference compound. In the case of 4-hydroxysulfadiazine, the majority of possible isomers could be discounted after H/D exchange. Substructure-specific MS/MS experiments with fragment ions and comparison with product ion spectra of two references revealed the presence of 4-hydroxysulfadiazine. The minor metabolite was characterized to some degree using H/D exchange and tandem mass spectrometry in combination with a high-resolution time of flight mass spectrometer. The aminopyrimidine moiety contained an additional modification with a likely elemental composition of . Antibiotics and antimicrobial agents are used for both therapeutic and prophylactic purposes in addition to their application as growth promoters. The antimicrobial sulfonamides are one class of pharmaceuticals that is widely used. As a consequence, these compounds have been found in surface and ground water, liquid manure, and soil [3][4][5][6][7][8][9][10][11][12]. After administration to animals, the majority of the pharmaceuticals used are excreted unchanged or as phase I and phase II metabolites. As part of an environmental risk assessment, these metabolites also have to be characterized because phase I metabolites can still be active against bacteria and phase II metabolites can be converted back to the parent drug or phase I metabolites. Moreover, very little is known about the capacity of microbiological decay and the occurrence of new metabolites after incubation for several months in a manure tank.There are only a few references describing the metabolism of sulfadiazine in pigs [13,14]. After intravenous administration of 40 to 60 mg sulfadiazine per kg body weight to male pigs without coadministration of trimethoprim, only low levels of metabolites have been observed. The N-acetyl sulfadiazine was the main metabolite in plasma. Traces of 4-hydroxysulfadiazine were also detected. N-acetyl sulfadiazine and 4-hydroxysulfadiazine were the major metabolites in urine collected up to three hours after application. No further metabolites were identified and investigations in feces were not carried out.The aim of the present work was to use different mass spectrometric strategies to identify possible metabolites of the widely used drug sulfadiazine in manure originating from a pig farm. The metabolites of interest should still have a similar structure as the parent drug and, therefore, retain to a greater or lesser extent their bioactive profile against micro-organisms. Earlier investigations about the biological activity of metabolites showed action of hydroxylated metabolites of sulfadiazine ag...

show abstract

Section: H/d Exchangementioning

confidence: 99%

Structural characterization of sulfadiazine metabolites using H/D exchange combined with various MS/MS experiments

Pfeifer¹,

Tuerk

Fuchs³

2005

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

Current literature in mass spectrometry

2003

J. Mass Spectrom.

View full text Add to dashboard Cite

In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books, Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (4 Weeks journals ‐ Search completed at 4th. June. 2003)

show abstract

Cathepsin K

Kirschke¹

2007

xPharm: The Comprehensive Pharmacology Reference

View full text Add to dashboard Cite

Complementary use of ion trap/time-of-flight mass spectrometry in combination with capillary high-pressure liquid chromatography: early characterization of in vivo metabolites of the cathepsin K inhibitor NVP-AAV490 in rat

Cited by 3 publications

References 15 publications

Structural characterization of sulfadiazine metabolites using H/D exchange combined with various MS/MS experiments

Structural characterization of sulfadiazine metabolites using H/D exchange combined with various MS/MS experiments

Current literature in mass spectrometry

Cathepsin K

Contact Info

Product

Resources

About