Liquid chromatographic-mass spectrometric studies on the enzymatic degradation of gonadotropin-releasing hormone.
Gonadotropin-releasing hormone (GnRH) derivatives are used in cancer therapy, but relatively little is known about their metabolic fate in the organism. This paper describes the application of high-performance liquid chromatography combined with electrospray mass spectrometry to identify the degradation products resulting from the incubation of two GnRH analogues, D-Phe6-GnRH and DSer(OtBu)6-desGly10-GnRH-ethylamide (buserelin) with rat kidney membranes. Reversed-phase columns were applied with gradient elution using a flow-rate of ca. 2 microliters/min to the mass spectrometer. Post- and precolumn stream splitting were employed to adjust the flow-rates for columns of 2 and 0.32 mm I.D. The pattern of peptide degradation products obtained with this method indicates that a defined proteolytic membrane enzyme system is responsible for these catabolic processes.
Brudel
M
M
Institute of Molecular Pharmacology, Berlin, Germany.
Kertscher
U
U
Berger
H
H
Mehlis
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002064:Buserelin / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D002853:Chromatography, Liquid / Q000379:methods*; D004798:Enzymes / Q000378:metabolism*; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods*; D008969:Molecular Sequence Data; D051381:Rats
D004798:Enzymes; D007987:Gonadotropin-Releasing Hormone; D002064:Buserelin