## 3 Metabolic Profiling of Urine: Recent Trends
### MEPS and SPME Advantages for the Metabolic Profile of Urine
#### 3.2.2 Oncologic Diseases (ODs)  
ODs are complex diseases triggered by different conditions and circumstances, but inevitably start with a cell that lost its normal homeostasis and started proliferating without control. These abnormal cells possess dramatically affected metabolisms, particularly at the glycolysis level (the \"Warburg effect\"), which they use to produce the amino acids, nucleotides and lipids necessary for their proliferation [114]. ODs will therefore produce changes that can be measured, whether they are changes in the abundance of certain compounds or new metabolites. Regarding this, the application of SPME to identify VOCs is a popular approach and has been successfully applied mainly to the characterization of the exhaled breath of cancer patients, particularly lung and breast cancer (reviewed in [PERSON] _et al._[13]), but also urine. This is supported by several experimental observations, particularly the olfactory detection of prostate cancer by dogs sniffing urine [115]. Further evidences were obtained using SPME-GC/MS to characterize the urinary VOCs signatures for different forms of cancer, including lung [85], breast [40], lymphoma, leukemia and colorectal cancer [89] and prostate [86]. In most of these cases, a relevant part of the VOCs signatures is caused by oxidative damage, as in the case of the aliphatic hydrocarbons, such as the aldehydes ethane and pentane, which are the main by-products of lipid peroxidation and oxidative DNA damage. This observation is supported by epidemiological evidence that clearly points to oxidative damage as one of the major sources of carcinogenesis [116]. However, as highlighted by [PERSON] and [PERSON] [117], although some urinary disease-associated VOCs have been used in clinics, more experimental work is necessary to consistently demonstrate the strength of some of those applications. Regarding this, [PERSON] _et al._[88] developed a fast SPME/GC-QqQ (triple quadrupole)-MS methodology to quantify three catecholamines metabolites (homovanillic acid (HMA), vanilmandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA)). Catecholamines, particularly noradrenaline, adrenaline and dopamine, are important neurotransmitters in the sympathetic nervous system, exerting cardiovascular and metabolic effects through adrenergic receptors stimulation in a wide variety of cells [118]. Their quantification is used in the diagnosis and management of patients with neurocrine tumors, such as phaeochromocytoma, and therefore, the application of this methodology in the clinical environment will have a major impact on the early diagnosis, disease progression and, in many cases, drug concentration, enabling important therapeutic drug monitoring (TDM) [13]. Additional works reporting the quantification of these catecholamines using MEPS and SPME are presented in Table 2[98, 99, 100]. In another direction, [PERSON] _et al._[90] used a fast and simple MEPS/LC-UV methodology to analyze the presence of oxidatively damaged DNA molecules in urine and reported that 8-oxodG levels are significantly augmented in breast and lung patients, while 5-HMUra is clearly less abundant in the urine from lung cancer patients in comparison to breast cancer and control samples. In turn, [PERSON] _et al._[119] reported that oxidative stress measured by urinary F2-isoprostane levels is associated with prostate cancer. This work, performed in an SPE/GC-MS format, shows the potential of F2-isoprostanes as biomarkers of prostate cancer. A microextraction approach applied to other ODs is therefore very pertinent and certainly will clarify if F2-isoprostane can be used as an OD biomarker.