http://dx.doi.org/10.1007/s00216-009-3247-1">
 

Document Type

Journal Article

Department/Unit

Department of Chemistry

Title

Improved liquid chromatography–tandem mass spectrometry method in clinical utility for the diagnosis of Cushing’s syndrome

Language

English

Abstract

Determination of urinary free cortisol is one of the first lines in screening for the diagnosis of Cushing's syndrome where its measurement is mostly done by immunoassay. Although easy to perform, immunoassays suffer from the problem of assay interferences and are unable to measure cortisone levels. To enhance such techniques for clinical diagnosis, an improved liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of urinary free cortisol and cortisone. The leftover urine samples from immunoassay were collected and subjected to facile solid-phase extraction cleanup. In the analysis of 130 urine samples from patients, 65 (50%) were found to have elevated urinary free cortisol (UFC) by immunoassay; but only 13 (10.8%) were found to have elevated UFC by this improved LC-MS/MS method. Nine out of the 13 patients, which showed elevated UFC by LC-MS/MS, were surgically confirmed to have Cushing's syndrome/disease. By setting a two times upper limit as a cut-off, the immunoassay gave a positive predictive value of 43.5%, whilst by using the improved method, a positive predictive value of 90% was obtained. Although several tests have been used extensively in first line screening for the diagnosis of Cushing's syndrome, none has ever shown with full capability of distinguishing all cases of Cushing's syndrome from normal and/or obese individuals. This method has shown superior analytical advantages over existing immunoassay type in terms of sensitivity, specificity and capability to diagnose Cushing's syndrome. Comparison between existing spectrometric methods, the reported developed method shown here, provides a simpler sample preparation procedure and meets with the high throughput demand of clinical laboratories. © 2009 Springer-Verlag.

Keywords

Cushing's syndrome, Immunoassay, Liquid chromatography-tandem mass spectrometry

Publication Date

2010

Source Publication Title

Analytical and Bioanalytical Chemistry

Volume

396

Issue

2

Start Page

783

End Page

790

Publisher

Springer Verlag

ISSN (print)

16182642

ISSN (electronic)

16182650

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