A study of low-molecular-weight organic acid urinary profiles in prostate cancer by a new liquid chromatography-tandem mass spectrometry method

• Published in: Journal of pharmaceutical and biomedical analysis 2018-09, Vol.159, p.229-236
• Main Authors: Klupczynska, Agnieszka, Plewa, Szymon, Sytek, Natalia, Sawicki, Wojciech, Dereziński, Paweł, Matysiak, Jan, Kokot, Zenon J.
• Format: Article
• Language: English
• Subjects: Benign prostatic hyperplasia; Liquid chromatography–mass spectrometry; Organic acids; Prostate cancer; Urine
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2018.06.059

[Display omitted] •Novel LC–MS/MS method for determination of organic acids in urine was developed.•Fast “dilute and shoot” sample preparation was applied.•The applicability of the methodology was proved on clinical urine samples. Metabolomic studies constantly require high throughput screenings, and this drives development and optimization of methods that include more analytes in a single run, shorten the analysis time and simplify sample preparation. The aim of the study was to develop a new simple and fast liquid chromatography-tandem mass spectrometry-based methodology for quantitative analysis of a panel of ten organic acids in urine. The metabolites selected for the study include ten molecules potentially associated with cancer development. Chromatographic separation involved a Phenomenex Synergi Hydro-RP column under gradient conditions. Quantitation of the analytes was performed in multiple reaction monitoring mode under negative ionization. Validation parameters were satisfactory and in line with the international guidelines. The methodology enabled us to analyze urine samples collected from prostate cancer (PC) (n = 49) and benign prostate hyperplasia (BPH) (n = 49) patients. The obtained concentrations were normalized with urinary specific gravity (USG) prior to statistical analysis. Five analytes were quantified in all urine samples and we observed the following USG-normalized concentration ranges: citric acid (146.5–6339.8), 3-hydroxyisobutyric acid (22.5–431.7), 2-ketoglutaric acid (4.4–334.4), lactic acid (10.1–786.3), succinic acid (4.1–500.5). 3-hydroxyisobutyric acid significantly decreased between two groups of prostate cancer patients: ≥7 Gleason patients and