Quantification of free and total desmosine and isodesmosine in human urine by liquid chromatography tandem mass spectrometry: A comparison of the surrogate-analyte and the surrogate-matrix approach for quantitation

Sara Ongay, Gert Hendriks, Jos Hermans, Maarten van den Berge, Nick H.T. ten Hacken, Nico C. van de Merbel, Rainer Bischoff*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)

Abstract

In spite of the data suggesting the potential of urinary desmosine (DES) and isodesmosine (IDS) as biomarkers for elevated lung elastic fiber turnover, further validation in large-scale studies of COPD populations, as well as the analysis of longitudinal samples is required. Validated analytical methods that allow the accurate and precise quantification of DES and IDS in human urine are mandatory in order to properly evaluate the outcome of such clinical studies. In this work, we present the development and full validation of two methods that allow DES and IDS measurement in human urine, one for the free and one for the total (free+peptide-bound) forms. To this end we compared the two principle approaches that are used for the absolute quantification of endogenous compounds in biological samples, analysis against calibrators containing authentic analyte in surrogate matrix or containing surrogate analyte in authentic matrix. The validated methods were employed for the analysis of a small set of samples including healthy never-smokers, healthy current-smokers and COPD patients. This is the first time that the analysis of urinary free DES, free IDS, total DES, and total IDS has been fully validated and that the surrogate analyte approach has been evaluated for their quantification in biological samples. Results indicate that the presented methods have the necessary quality and level of validation to assess the potential of urinary DES and IDS levels as biomarkers for the progression of COPD and the effect of therapeutic interventions.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalJournal of Chromatography A
Volume1326
Early online date18-Dec-2013
DOIs
Publication statusPublished - 24-Jan-2014

Keywords

  • COPD
  • Desmosine
  • Internal standard
  • Surrogate analyte
  • Surrogate matrix
  • Validation
  • OBSTRUCTIVE PULMONARY-DISEASE
  • ELASTIN DEGRADATION
  • LC-MS/MS
  • INTERNAL STANDARD
  • METHOD VALIDATION
  • REAL SAMPLES
  • BIOMARKERS
  • PLASMA
  • LUNG

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