Fast Atom Bombardment Mass Spectrometric Determination of the Molecular Weight Range of Uremic Compounds that Displace Phenytoin from Protein Binding: Absence of Midmolecular Uremic Toxins
作者:
Amitava Dasgupta,
Sohail Malik,
期刊:
American Journal of Nephrology
(Karger Available online 1994)
卷期:
Volume 14,
issue 3
页码: 162-168
ISSN:0250-8095
年代: 1994
DOI:10.1159/000168708
出版商: S. Karger AG
关键词: Fast atom bombardment mass;spectrometry Molecular weight range;uremic compounds;Phenytoin;Protein binding
数据来源: Karger
摘要:
Uremic compounds are known to displace phenytoin from protein binding, resulting in a higher concentration of the pharmacologically active free fraction of phenytoin. The true chemical identities and molecular weight range of all these compounds are still unknown. We demonstrated that indoxyl sulfate and hippuric acid, which are found at high concentrations in uremic patients, can only partially explain the elevated free phenytoin concentration. Other known uremic compounds, guanidine, methylguanidine, and guanidinosuccinic acid, do not displace phenytoin from the protein-binding sites. Uremic compounds from sera of patients on maintenance hemodialysis were removed using activated charcoal. These compounds were then backextracted from activated charcoal using methanol and analyzed by fast atom bombardment mass spectroscopy. Mass spectra of uremic sera showed no peak over m/z 450, indicating that midmolecular uremic toxins are not involved in displacing phenytoin from protein binding. We also observed additional peaks in the mass spectrum of uremic compounds when compared with the normal serum extract, indicating the presence of several endogeneous compounds in uremic sera, as expected.
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