Mass spectrometry tissues

Yanes O, Woo H, Northen T, Oppenheimer S, Shriver L, Apon J, Estrada M, Potchoiba M, Steenwyk R, Manchester M, Siuzdak G (2009) Nanostructure initiator mass spectrometry tissue imaging and direct biofluid analysis. Anal Chem 81 2969-2975. doi 10.1021/ ac802576q... 

In order to reduce or eliminate off-line sample preparation, multidimensional chromatographic techniques have been employed in these difficult analyses. LC-GC has been employed in numerous applications that involve the analysis of poisonous compounds or metabolites from biological matrices such as fats and tissues, while GC-GC has been employed for complex samples, such as arson propellants and for samples in which special selectivity, such as chiral recognition, is required. Other techniques include on-line sample preparation methods, such as supercritical fluid extraction (SFE)-GC and LC-GC-GC. In many of these applications, the chromatographic method is coupled to mass spectrometry or another spectrometiic detector for final confirmation of the analyte identity, as required by many courts of law. 

GC/MS has been employed by Demeter et al. (1978) to quantitatively detect low-ppb levels of a- and P-endosulfan in human serum, urine, and liver. This technique could not separate a- and P-isomers, and limited sensitivity confined its use to toxicological analysis following exposures to high levels of endosulfan. More recently, Le Bel and Williams (1986) and Williams et al. (1988) employed GC/MS to confirm qualitatively the presence of a-endosulfan in adipose tissue previously analyzed quantitatively by GC/ECD. These studies indicate that GC/MS is not as sensitive as GC/ECD. Mariani et al. (1995) have used GC in conjunction with negative ion chemical ionization mass spectrometry to determine alpha- and beta-endosulfan in plasma and brain samples with limits of detection reported to be 5 ppb in each matrix. Details of commonly used analytical methods for several types of biological media are presented in Table 6-1. 

Several methods are available for the analysis of trichloroethylene in biological media. The method of choice depends on the nature of the sample matrix cost of analysis required precision, accuracy, and detection limit and turnaround time of the method. The main analytical method used to analyze for the presence of trichloroethylene and its metabolites, trichloroethanol and TCA, in biological samples is separation by gas chromatography (GC) combined with detection by mass spectrometry (MS) or electron capture detection (ECD). Trichloroethylene and/or its metabolites have been detected in exhaled air, blood, urine, breast milk, and tissues. Details on sample preparation, analytical method, and sensitivity and accuracy of selected methods are provided in Table 6-1. 

Kucuk, O. et al.. Effects of lycopene supplementation in patients with localized prostate cancer, Exp. Biol. Med. (Maywood), 227, 881, 2002. van Breemen, R.B. et al.. Liquid chromatography-mass spectrometry of cis- and all-trans-lycopene in human serum and prostate tissue after dietary supplementation with tomato sauce, J. Agric. Food Chem., 50, 2214, 2002. 

Calcium exists in the human body as Ca(II) protein-bound and free Ca (II) ions (Dilana et al. 1994). For total extracellular Ca in plasma, serum and urine a definitive isotope dilution-mass spectrometry (ID-MS) method exist. Free Ca(II) in plasma/serum can be determined with PISE, but no definitive and reference methods exist. For Ca in faeces, tissue and blood flame atomic absorption (FAAS) is used widely. 

When pushed to the limit by overriding human health concerns, residue chemists have achieved detection limits of Ippt (Ingkg ) or even into the low ppqr (1 pg kg ) range. An example at the 1 ppt level is provided by methods for 2,3,7,8-tetrachlorodibenzodioxin (TCDD) in milk and TCDD in adipose tissue. Eor relatively clean matrices such as water and air, preconcentration on solid-phase adsorbents followed by GC or gas chromatography/mass spectrometry (GC/MS) can provide detection limits of 1 ng m and less for air (examples in Majewski and Capel ) and 1 ngL and less for water (examples in Larson et A summary of units of weight and concentration used to express residue data is given in Table 1. 

Specifically for triazines in water, multi-residue methods incorporating SPE and LC/MS/MS will soon be available that are capable of measuring numerous parent compounds and all their relevant degradates (including the hydroxytriazines) in one analysis. Continued increases in liquid chromatography/atmospheric pressure ionization tandem mass spectrometry (LC/API-MS/MS) sensitivity will lead to methods requiring no aqueous sample preparation at all, and portions of water samples will be injected directly into the LC column. The use of SPE and GC or LC coupled with MS and MS/MS systems will also be applied routinely to the analysis of more complex sample matrices such as soil and crop and animal tissues. However, the analyte(s) must first be removed from the sample matrix, and additional research is needed to develop more efficient extraction procedures. Increased selectivity during extraction also simplifies the sample purification requirements prior to injection. Certainly, miniaturization of all aspects of the analysis (sample extraction, purification, and instrumentation) will continue, and some of this may involve SEE, subcritical and microwave extraction, sonication, others or even combinations of these techniques for the initial isolation of the analyte(s) from the bulk of the sample matrix. 

Embrechts, J. Lemiere, F. Dongen, W. V. Esmans, E. L. Buytaert, P. van Marck, E. Kockx, M. Makar, A. Detection of estrogen DNA-adducts in human breast tumor tissue and healthy tissue by combined nano LC-nano ES tandem mass spectrometry. J. Am. Soc. Mass Spec from. 2003, 14, 482M-91. 

Tissue, B. M., Scimedia Mass Spectrometry Ionization Methods, accessed 3/9/2000, http //www.scimedia.com/chem-ed/ms/ftms.htm. 

Homish, R. E. and Wiest, J. R., Quantitation of spectinomycin residues in bovine tissues by ion-exchange high-performance liquid chromatography with post-column derivatization and confirmation by reversed-phase high performance chromatography-atmospheric pressure chemical ionization tandem mass spectrometry, /. Chromatogr. A, 812, 123, 1998. 

This procedure was compared with sequential extractive techniques employing alkaline hydrolysis of dried plant tissue followed by extraction of the acidified mixture with ethyl acetate. Fractions were individually evaluated for phytotoxic properties. Selected fractions from those showing a positive response were analyzed by gas-liquid chromatography. Structural identification and characterization of the individual components in these selected fractions were accomplished by gas chromatography-mass spectrometry. 

A recent series of experiments with cats, chickens, or rats exposed to [uniformly labeled 14C-phenyl]-TOCP shows that a complex array of oxidized and dearylated metabolites are found in excreta and various tissues including the liver, kidney, testis, and brain (Abou-Donia et al. 1990a, 1990b Nomeir and Abou-Donia 1986 Somkuti and Abou-Donia 1990). Cats and chickens, like humans, are sensitive to TOCP-induced delayed neuropathy (Baron 1981). A similar array of oxidized and dearylated derivatives of tri-para-cresyl phosphate (but no cyclic metabolites) were identified by mass spectrometry in the urine and... 

DeSouza, L., Diehl, G., Rodrigues, M.J., Guo, J., Romaschin, A.D., Colgan, T.J., Siu, K.W. (2005). Search for cancer markers from endometrial tissues using differentially labeled tags iTRAQ and cICAT with multidimensional liquid chromatography and tandem mass spectrometry. J. Proteome Res. 4, 377-386. 

Shi S-R, Liu C, Balgley BM, et al. Protein extraction from formalin-fixed, paraffin-embedded tissue sections quality evaluation by mass spectrometry. I. Histochem. 

When fresh or frozen tissue is used for proteomic analyses, the results cannot be related directly to the clinical course of diseases in a timely manner. Instead, researchers frequently reduce the number of interesting proteins to a manageable number and then attempt to use immunohistochemistry to understand the implications of proteomic changes in archival formalin-fixed, paraffin-embedded (FFPE) tissue for which the clinical course has been established.3 Unfortunately, immunohistochemistry is a semiquantitative pro-teomic method, and the choice of interesting proteins must occur without advance knowledge of the clinical course of the disease or the response to therapy. If routinely fixed and embedded archival tissues could be used for standard proteomic methods such as 2-D gel electrophoresis and mass spectrometry (MS), these powerful techniques could be used to both qualitatively and quantitatively analyze large numbers of tissues for which the clinical course has been established. However, analysis of archival FFPE tissues by... 

Chaurand P, Stoeckli M, Caprioli RM. Direct profiling of proteins in biological tissue sections by MALDI mass spectrometry. Anal. Chem. 1999 71 5263-5270. 

Stewart NA, Veenstra TD. Sample preparation for mass spectrometry analysis of formalin-fixed paraffin-embedded tissue proteomic analysis of formalin-fixed tissue. Methods Mol. Biol. 2008 425 131-138. 

There have been no comprehensive studies of how exposure to ethanol, xylene, or paraffin affects proteins following their treatment with aqueous formaldehyde. However, in a related study, Rait et al.25 examined the effect of ethanol incubation on 2 -deoxyadenosine that had been treated with aqueous formaldehyde. Mass spectrometry revealed the presence of N6-ethoxymethyl adducts in addition to hydroxymethyl adducts. This lead to the suggestion that tissue dehydration can result in molecular dehydration, transforming hydroxymethyl groups into Schiff-bases. In such a scheme, the bulk anhydrous ethanol acts as a medium to effectively absorb the water of the... 

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