title: Determination of polyamine metabolome in plasma and urine by ultrahigh performance liquid chromatography-tandem mass spectrometry method: application to identify potential markers for human hepatic cancer.
abstract: To evaluate the potential relationship between cancer and polyamine metabolome, a UHPLC-MS/MS method has been developed and validated for simultaneous determination of polyamine precursors, polyamines, polyamine catabolite in human plasma and urine. Polyamine precursors including L-ornithine, lysine, L-arginine and S-adenosyl-L-methionine; polyamines including 1,3-diaminopropane, putrescine, cadaverine, spermidine, spermine, agmatine, N-acetylputrescine, N-acetylspermine and N-acetylspermidine; polyamine catabolite including γ-aminobutyric acid had been determined. The analytes were extracted from plasma and urine samples by protein precipitation procedure, and then separated on a Shim-pack XR-ODS column with 0.05% heptafluorobutyric acid (HFBA) in methanol and 0.05% HFBA in water. The detection was performed on UHPLC-MS/MS system with turbo ion spray source in the positive ion and multiple reaction-monitoring mode. The limits of quantitation for all analytes were within 0.125-31.25 ng mL(-1) in plasma and urine. The absolute recoveries of analytes from plasma and urine were all more than 50%. By means of the method developed, the plasma and urine samples from hepatic cancer patients and healthy age-matched volunteers had been successfully determined. Results showed that putrescine and spermidine in hepatic cancerous plasma were significant higher than those in healthy ones, while spermidine, spermine and N-acetylspermidine in hepatic cancerous urine were significant higher than those in healthy ones. The methods demonstrated the changes of polyamine metabolome occurring in plasma and urine from human subjects with hepatic cancer. It could be a powerful manner to indicate and treat hepatic cancer in its earliest indicative stages.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Ran
authors.initials: R
authors.lastname: Ma
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Lin
authors.forename: Huarong
authors.initials: H
authors.lastname: Xu
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D055442:Metabolome; D011073:Polyamines / Q000097:blood* / Q000652:urine*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D011073:Polyamines
keywords: Cancer biomarker; HFBA; Hepatic cancer; IS; MRM; Plasma and urine; Polyamine metabolome; UHPLC–MS/MS; heptafluorobutyric acid; internal standard; multiple reaction-monitoring; ultrahigh performance liquid chromatography–tandem mass spectrometry