title: Quantitation of desmosine and isodesmosine in urine, plasma, and sputum by LC-MS/MS as biomarkers for elastin degradation.
abstract: The aim of this study is to develop a standardized LC-MS/MS method for accurate measurement of desmosine (DES) and isodesmosine (IDS) in all body fluids as biomarkers for in vivo degradation of matrix tissue elastin in man and animals. A reproducible three-step analytical procedure: (1) sample hydrolysis in 6N HCl, (2) SPE by a CF1 cartridge with addition of acetylated pyridinoline as internal standard (IS), and (3) LC/MSMS analysis by SRM monitoring of transition ions; DES or IDS (m/z 526-481+397) and IS (m/z 471-128) was developed. The method achieves accurate measurements of DES/IDS in accessible body fluids (i.e. urine, plasma, and sputum). LOQ of DES/IDS in body fluids is 0.1 ng/ml. The % recoveries and reproducibility from urine, plasma, and sputum samples are above 99 ± 8% (n = 3), 94 ± 9% (n = 3) and 87 ± 11% (n = 3), with imprecision 8%, 9% and 10%, respectively. The proposed method was applied to measure DES/IDS in body fluids of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Total DES/IDS in sputum and plasma is increased over normal controls along with the free DES/IDS in urine in patients. DES/IDS can be used to study the course of COPD and the response to therapy. This practical and reliable LC-MS/MS method is proposed as a standardized method to measure DES and IDS in body fluids. This method can have wide application for investigating diseases which involve elastic tissue degradation.
authors.affiliation: Department of Medicine, St. Luke's Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY 10019, USA.
authors.forename: Shuren
authors.initials: S
authors.lastname: Ma
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Turino
authors.forename: Yong Y
authors.initials: YY
authors.lastname: Lin
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D003895:Desmosine / Q000032:analysis* / Q000097:blood / Q000652:urine; D004549:Elastin / Q000378:metabolism*; D006801:Humans; D006851:Hydrochloric Acid; D006868:Hydrolysis; D007524:Isodesmosine / Q000032:analysis* / Q000097:blood / Q000652:urine; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000652:urine; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013183:Sputum / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D003895:Desmosine; C015484:pyridinoline; D004549:Elastin; D007524:Isodesmosine; D006851:Hydrochloric Acid