Chemical-ionization mass spectrometry sensitivity

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. 

R. Chaler, J. O. Grimalt, C. Pelejero, and E. Calvo, Sensitivity Effects in U 7 Paleotemperature Estimation by Chemical Ionization Mass Spectrometry, Anal. Chem. 2000, 72, 5892. 

A flow diagram of our extraction procedure is shown in Figure 1. We find that this procedure provides adequate clean-up and recovery of the THC in the least amount of time (3). However, it should be stated that the degree of clean-up achieved by this procedure is adequate primarily because we are using chemical ionization mass spectrometry to measure the ratio of labeled to unlabeled A-THC. In our experience chemical ionization often affords better sensitivity and specificity than electron impact ionization. For rea-... 

Chaler R., Grimalt J. O., Pelejero C., and Calve E. (2000) Sensitivity effects in UII7 paleotemperature estimation by chemical ionization mass spectrometry. Anal. Chem. 72, 5892-5897. 

Napoli et al. (23) developed a sensitive assay based on negative chemical ionization mass spectrometry to quantify retinoic acid in human plasma. Endogenous levels of all trans retinoic acid in plasma were 4.9 ng/ml, using a 0.1 ml sample. The limit of detection was less than 1 ng/ml. Direct quantification of 13-cis retinoic acid was impossible due to the inability of the GC to resolve the isomers. Barua and Olson (33) described a method to quantify all trans retinoic acid in serum using reverse phase HPLC. They detected 1.8 ng/ml of the all trans isomer, using a 2 ml serum sample and a non-acidic extraction procedure. 

Two general methods utilizing the stable isotope dilution technique have been successfully used for the quantification of drugs and their metabolites by ms. The simplest, but least sensitive and specific method, is a non-chromatographic technique that utilizes chemical ionization mass spectrometry (cims) and internal standards labeled with stable isotopes. This method has been used to quantify the antiarrhythmic drugs, lidoq lne and quinidine and some of their metabolites, in human plasma samples. 

Derivatization is also useful to detect volatile metabolites. Liu et al. [282] described a specific, rapid, and sensitive in situ derivatization solid-phase microextraction (SPME) method for determination of volatile trichloroethylene (TCE) metabolites, trichloroacetic acid (TCA), dichloroacetic acid (DCA), and trichloroethanol (TCOH), in rat blood. The metabolites were derivatized to their ethyl esters with acidic ethanol, extracted by SPME and then analyzed by gas chromatography/negative chemical ionization mass spectrometry (GC-NCI-MS). After validation, the method was successfully applied to investigate the toxicokinetic behavior of TCE metabolites following an oral dose of TCE. Some of the common derivatization reagents include acetyl chloride and TV-methyl-iV- ft-b u (y Idi methyl si I y I) tro (1 uoroacctam i nc (MTBSTFA) for phenols and aliphatic alcohols and amines, dansyl chloride and diazomethane for phenols, dansyl chloride for amines, acidic ethanol and diazomethane for carboxylic acids, and hydrazine for aldehydes. 

Possibly as a result of the social implications of the hallucinogenic j5-phenethyl-amines and simple isoquinoline alkaloids, a large number of new plant species suspected to contain these structural types have been closely scrutinized with the aid of sensitive analytical methods. Thus, extensive screening of a large variety of cactus species has been carried out. G.c. analysis has indicated the presence of trace amounts of dimers and trimers of phenethylamine and tetrahydroiso-quinoline types " while combination g.c.-mass spectrometry has enabled rapid identification of alkaloids of 120 cactus species." High voltage electrophoresis has been used for quantitative alkaloid determination.Useful structural information may be obtained from the technique of chemical ionization mass spectrometry. ... 

Tanimoto, H., Hirokawa, J., Kajii, Y., and Akimoto, H., Characterization of gas chromatography/ negative ion chemical ionization mass spectrometry for ambient measurements of PAN potential interferences and long-term sensitivity drift, Geophys. Res. Lett., 27, 2089-2092, 2000. 

Perfluoroacyl derivatives such as trifluoroacetyl (TF.A), pentafluoropropionyl (PFP) and heptafluorobutyryl (HFB) are very commonly employed in GC-MS. Much of their popularity arose from their ease of preparation and their useful employment in GC with ECD. Workers then employed them directly in the GC-MS system and in many cases excellent results were obtained—high mass increments which can be conveniently adjusted by choice of derivative (see Table 3) and high abundance fragment ions. All this is in addition to their advantages for negative-ion chemical ionization mass spectrometry, where their electron capturing properties can enable highly sensitive analyses to be carried out. 

Higashi, T. Takido, N. Yamauchi, A. Shimada, K. Electron-capturing derivatization of neutral steroids for increasing sensitivity in liquid chromatography/negative atmospheric pressure chemical ionization-mass spectrometry. Anal. Sci. 2002,18 (12), 1301-1307. 

Richon G, Paris C, Girardin M, et al. Highly sensitive, quick and simple quantification method for mono and disaccharides in aqueous media using liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS). J Chromat B. 2011 879 1529-36. 

Martens-Lobenhoffer, J. Banditt, P. Sensitive and specific determination of clindamycin in human serum and bone tissue applying liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry, J.Chromatogr.B, 2001, 755, 143-149. 

Rudewicz, P. Munson, B. Effect of Ammonia Partial Pressure on the Sensitivities for Oxygenated Compounds in Ammonia Chemical Ionization Mass Spectrometry. Anal. Chem. 1986, 58, 2903-2907. 

Tenberken, O., Worek, F., Thiermann, H., et al., 2010. Development and validation of a sensitive gas chromatography-ammonia chemical ionization mass spectrometry method for the determination of tabun enantiomers in hemo-lysed blood and plasma of different species. J. Chromatogr. B 878,1290-1296. 

Seto, Y, Kanamori-Kataoka, M., Tsuge, K., et al, 2013. Sensitive monitoring of volatile chemical warfare agents in air by atmospheric pressure chemical ionization mass spectrometry with counter-flow introduction. Anal. Chem. 

Laser ionization mass spectrometry or laser microprobing (LIMS) is a microanalyt-ical technique used to rapidly characterize the elemental and, sometimes, molecular composition of materials. It is based on the ability of short high-power laser pulses (-10 ns) to produce ions from solids. The ions formed in these brief pulses are analyzed using a time-of-flight mass spectrometer. The quasi-simultaneous collection of all ion masses allows the survey analysis of unknown materials. The main applications of LIMS are in failure analysis, where chemical differences between a contaminated sample and a control need to be rapidly assessed. The ability to focus the laser beam to a diameter of approximately 1 mm permits the application of this technique to the characterization of small features, for example, in integrated circuits. The LIMS detection limits for many elements are close to 10 at/cm, which makes this technique considerably more sensitive than other survey microan-alytical techniques, such as Auger Electron Spectroscopy (AES) or Electron Probe Microanalysis (EPMA). Additionally, LIMS can be used to analyze insulating sam-... 

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