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 degrada...

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Bibliographic Details
Published in:Journal of Chromatography A 1994-02, Vol.661 (1), p.55-60
Main Authors: Brudel, M., Kertscher, U., Berger, H., Mehlis, B.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Buserelin - metabolism
Cell Membrane - enzymology
Chromatography, Liquid - methods
Enzymes - metabolism
Gonadotropin-Releasing Hormone - analogs & derivatives
Gonadotropin-Releasing Hormone - metabolism
Kidney - enzymology
Kinetics
Mass Spectrometry - methods
Molecular Sequence Data
Rats
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Summary: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-Phe 6-GnRH and dSer(OtBu) 6-desGly 10-GnRH-ethylamide (buserelin) with rat kidney membranes. Reversed-phase columns were applied with gradient elution using a flow-rate of ca. 2 μl/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.
ISSN:0021-9673
DOI:10.1016/0021-9673(94)85177-8