A short review of applications of liquid chromatography mass spectrometry based metabolomics techniques to the analysis of human urine

Abstract

The applications of metabolomics as a methodology for providing better treatment and understanding human disease continue to expand rapidly. In this review, covering the last two years, the focus is on liquid chromatography-mass spectrometry (LC-MS) profiling of metabolites in urine. In LC-MS based metabolomics there are still problems with regard to: chromatographic separation, peak picking and alignment, metabolite identification, metabolite coverage, instrument sensitivity and data interpretation and in the case of urine sample normalisation. Progress has been made with regard to all of these issues during the period of the review. Of particular interest are the increasing use of orthogonal chromatographic methods for optimal metabolite coverage and the increasing adoption of receiver operator characteristic (ROC) curves for biomarker validation.

Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2′-deoxyguanosine by UPLC-MS/MS Analysis

“…These indicate that the level of 8-OHdG in urine could be a good indicator of oxidative damage to DNA in the whole body. Although some urinary chemical constituents are affected by diet, exercise, hormone status and other physiological conditions, and high concentrations of urea and inorganic salts (chloride, sodium, and potassium) in urine may result in ionization source contamination and ion suppression in mass spectrometry detection, compared with other biological matrices such as plasma, serum and saliva, urine has long been considered to be a preferred diagnostic biofluid in clinical practice since it is sterile, easily obtainable in large volumes, and noninvasive to patients272829303132. Therefore, urinary 8-OHdG analysis should be the first choice for disease risk evaluation, early detection, treatment and prognosis.…”

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

“…Various normalization methods have been used and published to address this issue, including the traditional use of urinary creatinine concentration, osmolality,30, 31 total useful MS signal,30 and specific gravity19, 32 as well as a combination of creatinine concentration and normalization of the MS signal20 and the determination of the total concentration of chemically labeled metabolites by using liquid chromatography‐ultraviolet 33. However, many studies do not use normalization procedures, and there is still no consensus on this point 34. We employed a MSTUS normalization strategy,19, 31 which uses the total intensity of metabolites that are common to all samples and which is easy to implement and was found to perform better than creatinine normalization 20.…”

<italic>Mup</italic>-knockout mice generated through CRISPR/Cas9-mediated deletion for use in urinary protein analysis

“…Major bioactive excreta reported in urine include metabolites, non-coding RNA molecules, and proteins. Metabolomics analyses have revealed more than 2000 metabolites in mouse urine [20]. Small volatile organic compounds have been studied as potential biomarkers of lung cancer in a recent study [21].…”