title: 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.
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.
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Sara
authors.initials: S
authors.lastname: Ongay
authors.affiliation: Bioanalytical Laboratory, PRA, Early Development Services, Westerbrink 3, 9405 BJ Assen, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Hendriks
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Hermans
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Pulmonology, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
authors.forename: Nick H T
authors.initials: NH
authors.lastname: ten Hacken
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands; Bioanalytical Laboratory, PRA, Early Development Services, Westerbrink 3, 9405 BJ Assen, The Netherlands.
authors.forename: Nico C
authors.initials: NC
authors.lastname: van de Merbel
authors.affiliation: University of Groningen, Department of Pharmacy, Analytical Biochemistry, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: r.p.h.bischoff@rug.nl.
authors.forename: Rainer
authors.initials: R
authors.lastname: Bischoff
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D002138:Calibration; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003895:Desmosine / Q000652:urine*; D005260:Female; D006801:Humans; D007524:Isodesmosine / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000652:urine; D029424:Pulmonary Disease, Chronic Obstructive / Q000652:urine; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D010455:Peptides; D003895:Desmosine; D007524:Isodesmosine
keywords: COPD; Desmosine; Internal standard; Surrogate analyte; Surrogate matrix; Validation