Blood analysis, mass spectrometer

Danaceau JP, Anderson GM, McMahon WM, Crouch DJ. 2003. A liquid chromatographic-tandem mass spectromet-ric method for the analysis of serotonin and related indoles in human whole blood. J Anal Toxicol 27 440. 

Benjamin Tan, L.L., Mustafa, A.M., 2003. Analysis of selected pesticides and alkylphenols in human cord blood by gas chromatograph-mass spectrometer. Talanta 61, 385-391. 

In thermal ionization mass spectrometry (TI-MS), solid, inorganic compounds may be volatilized from a heated surface. TI-MS is the most precise method for the measurement of isotopic ratios of minerals and has been used to analyze 58pe in fecal samples collected from a human study (H). The major drawbacks of this technique are the costly instrument and the slow sample through-put. Conventional mass spectrometry produces ions by electron bombardment of the vapor of volatile compoimds. This is called electron-impact ionization mass spectrometry (EI-MS). Analysis of iron by EI-MS requires derivitization to volatile forms before introduction into the mass spectrometer. A method has been developed for the synthesis of volatile iron-acetylacetone chelates from iron in blood serxm (1 ). A tetraphenylporphyrin chelate has also been synthesized and used in an absorption study in which 54pe and 57pe were given orally (16). 

Fig. (1). Peptidomics strategies used to study Drosophila immunity. (A) Using antimicrobial assays (antibacterial and antifungal), the bioactive peptides were isolated from the blood of bacteria-challenged Drosophila. MS was used for molecular mass assignment, to identify post-translational modifications, and for primary structure elucidation (B) Identification of peptidic immune effectors through differential display analysis (DD) by MALDI-MS and micro/nano RP-HPLC coupled (online) or not (off-line) to ESI-MS. When the HPLC was performed off-line to the mass spectrometer, fractions were individually analyzed by MALDI-MS. The identification and the structural characterization were performed either by molecular mass assignment and/or sequencing by ESI-MS/MS.

Figure 8 General experimental setup for the on-line analysis of drugs in the blood of a live rat. The dialysate from a microdialysis device implanted in the jugular vein of a rat is allowed to flow into the mass spectrometer at the CF— FAB interface.

At present researchers and clinicians interested in complete blood gas analysis must resort to different sets of instruments and techniques for each of the three types of measurement. This chapter describes a membrane permeation cell connected to a mass spectrometer that can measure blood gas partial pressures, contents, and the position of the 02 dissociation curve. 

There are several reviews in the literature on the theory and design of mass spectrometers (33, 34). A brief description of the operation as it relates to the blood gas analysis cell is presented here. 

Blood Gas Analysis Cell. The blood gases enter the mass spectrometer by permeation through a thin Teflon membrane enclosed in the blood gas cell (BGC). The design of the stirred BGC was determined by the following general requirements and constraints ... 

Several major advances that made GC a more attractive tool in blood hormone analysis took place during the last 10-15 years (a) development of more efficient, fast, and selective ways to purify plasma extracts, as based on the availability of various hpophilic gels and HPLC (b) availability of highly efficient capillary colunms to reduce the cases of co-elution of hormones with other mixture components (also, increasing detection sensitivity in most instances) and (c) a wider utilization of the mass spectrometer as a highly specific and sensitive GC detector. Several examples will now be shown to reinforce these points. 

The next level of complexity is the analysis of compounds in complex matrices such as blood plasma, biological tissues, or environmental samples. Here the class of compounds of interest needs to be recovered from the matrix using, for instance, solvent or solid phase extraction. The resulting extracts are usually still complex mixtures that are best separated chromatographically prior to introduction into the mass spectrometer. The polarity of the analytes will determine whether GC or LC is the appropriate technique. The versatility of QqQ instruments is particularly suited... 

Tandem MS is used to provide more information than can be afforded by a single mass spectrometer and is widely used for screening complex matrices such as blood and urine. Analysis is achieved, in effect, by performing two stages of SIM. The first mass spectrometer is set to transmit the precursor ion of interest into a region where fragmentation occurs. One of the product ions is monitored by a second mass spectrometer. Selection of an appropriate internal... 

The experimental conditions and the injection procedure were essentially the same as those in the irritation studies. Blood samples were collected from the ear vein at appropriate time intervals following treatment and centrifuged to obtain the serum for analysis. The extraction procedure of CPZ in the serum was performed according to the modified method of Mckay et al. (8). The quantification of CPZ was carried out on a gas chromatograph-mass spectrometer-computer system. The instrument was used in the selected ion monitoring mode. 

Answer GCMS. The HD detector would respond to ethanol (it is widely used for blood alcohol analysis), but the response is not specific. Since a complex pattern of peaks would be expected from such a sample, it would be difficult to definitively identify one as ethanol, although it would likely be one of the earliest eluting peaks. A mass spectrometer could provide definitive identification of ethanol via the com-p>ound s mass spectrum. 

As a result of the low concentration of flavanols in blood fractions such as plasma when food level doses are consumed, there are only a few techniques that have sufficient sensitivity. The first of these is gas chromatography coupled to a mass spectrometer for detection [88]. This technique is quite sensitive and provides the assurance of accurate identification of the analyte when the molecular and major fragmentation ions are monitored. The drawbacks are that it is necessary to derivatize the flavanols to achieve sufficient volatility and the technique cannot be adapted for analysis of glucuronide and sulfate conjugates. This method has been used to quantify the plasma levels of catechin and its methylated derivatives after wine consumption, and a modified version is able to detect catechin, quercetin, and resveratrol simultaneously [89]. 

Many metabolites are polar, ionic, and nonvolatile. Thus comprehensive metabolic analysis is not well suited for gas chromatographic techniques. Metabolite mixtures in complex biological samples such as lymph and blood, however, can be rapidly characterized by electrospray ionization with ion mobility coupled to mass spectrometry. As with GC-IMS, coupling ion mobility spectrometers with mass spectrometers produces two dimensions of information. There are many types of ion mobility-mass spectrometers (IM-MS) and most of these will be discussed in other chapters of this book. The focus of this chapter, however, is on atmospheric pressure IMS with quadrupole or time-of-flight mass spectrometry. Other types of IM-MS have also been recently been reviewed. Advantages of coupling atmospheric pressure IMS with a mass spectrometer include ... 

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