title: Determination of free desmosine and isodesmosine as urinary biomarkers of lung disorder using ultra performance liquid chromatography-ion mobility-mass spectrometry.
abstract: The elastin degradation products, desmosine (DES) and isodesmosine (IDES) are highly stable, cross-linking amino-acids that are unique to mature elastin. The excretion of DES/IDES in urine, in the free form and with associated peptide fragments, provides an indicator of lung damage in chronic obstructive pulmonary disease (COPD). A quantitative ion mobility-mass spectrometry (IM-MS) method has been developed for the analysis of free DES/IDES in urine with deuterated IDES as an internal standard. Resolution of DES/IDES isomers was achieved in less than five minutes using ultra performance liquid chromatography (UPLC) combined with ion pairing. The optimized UPLC-IM-MS method provided a linear dynamic range of 10-300 ng/mL and a limit of quantitation of 0.028 ng/mL for IDES and 0.03 ng/mL for DES (0.55 ng and 0.61 ng on column respectively). The method reproducibility (%RSD) was <4% for DES and IDES. The UPLC-IM-MS method was applied to the analysis of urine samples obtained from healthy volunteers and COPD patients. The DES/IDES concentrations in healthy and COPD urine showed an increase in DES (79%) and IDES (74%) in the COPD samples, relative to healthy controls. The incorporation of an IM separation prior to m/z measurement by MS was shown to reduce non-target ion responses from the bio-fluid matrix.
authors.affiliation: Centre for Analytical Science, Department of Chemistry, Loughborough University, Loughborough, Leicestershire, UK.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Devenport
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Ved
authors.initials: V
authors.lastname: Parkash
authors.forename: Jason
authors.initials: J
authors.lastname: Cook
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weston
authors.forename: Colin S
authors.initials: CS
authors.lastname: Creaser
mesh_terms: D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003895:Desmosine / Q000652:urine*; D005260:Female; D006801:Humans; D007524:Isodesmosine / Q000652:urine*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D029424:Pulmonary Disease, Chronic Obstructive / Q000652:urine*; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D003895:Desmosine; D007524:Isodesmosine