Hw. Li et al., Quantitative high performance liquid chromatography/ tandem mass spectrometric analysis of the four classes of F-2-isoprostanes in human urine, P NAS US, 96(23), 1999, pp. 13381-13386
Citations number
50
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Isoprostanes (iPs) are free radical catalyzed prostaglandin isomers. Analys
is of individual isomers of PGF(2 alpha)-F-2-iPs-in urine has reflected lip
id peroxidation in humans. However, up to 64 F-2-iPs may be formed, and it
is unknown whether coordinate generation, disposition, and excretion of F2-
iPs occurs in humans. To address this issue, we developed methods to measur
e individual members of the four structural classes of F2-iPs, using liquid
chromatography/tandem mass spectrometry (LC/MS/MS), in which sample prepar
ation is minimized. Authentic standards of F-2-iPs of classes Ill, IV, V, a
nd VI were used to identify class-specific ions for multiple reaction monit
oring. Using IPF2 alpha-VI as a model compound, we demonstrated the reprodu
cibility of the assay in human urine. Urinary levels of all F2-iPs measured
were elevated in patients with familial hypercholesterolemia. However, onl
y three of eight F-2-iPs were elevated in patients with congestive heart fa
ilure, compared with controls. Paired analyses by GC/MS and LC/MS/MS of IPF
2 alpha-VI in hypercholesterolemia and of 8,12-iso-iPF(2 alpha)-VI in conge
stive heart failure were highly correlated. This approach will permit high
throughput analysis of multiple iPs in human disease.