Positive electrospray ionization

Jenkins et al. developed a capillary electrophoresis system for the measurement of iohexol as a marker of the glomerular filtration rate (GFR) with a run time of 5.25 min and a coefficient of variation (CV) of 4.3% at 80 mg L" [121]. The GFR, calculated from the plasma clearance, had a reproducibility of 5.47 %. A similar approach (liquid chromatography-mass spectrometry with positive electrospray ionization after enrichment by solid phase extraction) was applied by Putschew et al. for the determination of iodinated contrast agents in treatment plant effluents and surface waters [118]. 

Table 7.1.1 Mass spectrometry fMSj settings for purine and pyrimidine screening in the positive electrospray ionization (ESI) mode, orotic acid in the negative ESI mode ... 

Song and Naidong [129] analyzed omeprazole and 5-hydroxyomepra-zole in human plasma using hydrophilic interaction chromatography with tandem mass spectrometry. Omeprazole and its metabolite 5-hydroxy omeprazole and the internal standard desoxyomeprazole were extracted from 0.05 ml of human plasma using 0.5 ml of ethyl acetate in a 96-well plate. A portion (0.1 ml) of the ethyl acetate extract was diluted with 0.4 ml of acetonitrile and 10 /il was injected onto a Betasil silica column (5 cm x 3 mm, 5 /rm) and detected by atmospheric pressure ionization 3000 and 4000 with positive electrospray ionization. Mobile phase with linear gradient elution consists of acetonitrile, water, and formic acid (from 95 5 0.1 to 73.5 26.5 0.1 in 2 min). The flow-rate was 1.5 ml/min with total rim time of 2.75 min. The method was validated for a low limit of quantitation at 2.5 ng/ml for both analytes. The method was also validated for specificity, reproducibility, stability, and recovery. 

A method has been proposed for the determination of cellular levels in lung cancer cell lines of the TKIs dasatinib and lapatinib [141], Cellular samples were extracted with a mixture of tert-butyl methyl ether/ACN/ammonium formate pH 3.5 (6 2 1, v/v/v). The organic layer was subjected to evaporation and the samples were reconstituted in acetonitrile, followed by chromatographic separation on a C18 column. Dasatinib and lapatinib were monitored by tandem MS equipped with a positive electrospray ionization interface in positive ion mode. These cellular experiments showed that lapatinib is not actively expelled from P-gp over-expressing cancer cells, while P-gp activity significantly decreases cellular levels of dasatinib [141],... 

The positive charge of QTA and the explicit proton affinity of TTA make these cationic compounds ideal candidates for mass spectrometric detection after positive electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). 

Fig. 5 Statistical evaluation of LC-MS-based methods for tropane alkaloids referred in this chapter. (a) Relative frequency of ionization methods. +APCI positive atmospheric pressure chemical ionization, +ESI positive electrospray ionization, FAB fast atom bombardment, +TSP positive thermospray, (b) Relative frequency of scan modes used. MS full scan MS, MS/MS tandem mass spectrometry (product ion scan), MRM multiple reaction monitoring, SIM selected ion monitoring, (c) Relative frequency of mass analysers used. EBQtQ2 double focusing sector field mass spectrometer, IT ion trap, QqQ triple quadrupole, SQ single quadrupole. Considered publications were found by PubMed data-based search and references cited in these articles...

Fig. 8 Product ion spectra of diverse tropane alkaloids after collision-induced dissociation. Spectra were obtained after positive electrospray ionization and collision-induced dissociation (CID) with nitrogen in a QTrap 4000 instrument. Common structural elements cause generation of corresponding diagnostic fragments, e.g. m/z 124 and 93. For structural assignment of biotransformation products similar fragmentation pattern were produced and interpreted as shown by Chen et al. [6, 7, 51] and He et al. [59]...

The positive electrospray ionization tandem mass spectrometry (ESTMS/ MS) of lornoxicam was obtained using an Agilent 6410 QQQ mass spectrometer with collision energy 10 eV using argon as collision gas and is shown in Fig. 6.14. Table 6.8 shows the mass fragmentation pattern of the drugs. 

The positive electrospray ionization (ESI) mass spectrum. Fig. (4), of xanthochymol (138) showed a base peak at [M + IIJ4 = m/z 603 and... 

Very recently, a polymer-supported construct for quantifying the reactivity of monomers involving multicomponent Ugi strategies was reported [53]. The authors investigated the Ugi four-component condensation of a set of aldehydes, acids, and isonitriles. The amine compound used was bound to a specially modified Rink amide polystyrene resin bearing an ionization leveler and bromine functionality as a mass splitter for accurate analysis by positive electrospray ionization mass spectrometry. The microwave-assisted experiment was performed with a set of ten carboxylic acids, hydrocinnamaldehyde, and cyclohexyl isonitrile in DCM-... 

Cherlet M, De Baere S, De Backer P, Quantitative analysis of oxytetracycline and its 4-epimer in calf tissues by liquid chromatography combined with positive electrospray ionization mass spectrometry, Ana/yi f 2003 128 871-878. 

The use of microbore columns in LC-MS system wifli positive electrospray ionization allowed enhanced sensitivity of MC determination. " In the system developed for determination of MC in water samples with 1 mm I.D. column and selected ion monitoring mode, and using sample preconcentration reported earlier on C18 cartridges, detection limits for MC-LR, -RR, and -YR were reported... 

Table 19.1 Ions monitored for determination of niacin by isotope dilution mass spectrometry using positive electrospray ionization. Both natural and labelled nicotinic acid are protonated in positive ion electrospray ionization, giving quasi-molecular ions at mass-to-charge ratios (m/z) of 124 and 128, respectively, which can be monitored directly in selected ion recording (SIR) experiments and selected as the parent ions in multiple reaction monitoring (MRM) experiments. In MRM experiments protonated nicotinic acid can be induced to produce daughter ions at several other m/z values, but the given transitions are the ones with the highest signal intensity.

Hyphenated techniques like GC-MS and LC-MS techniques are mainly used for identification of the compound and confirmation of its structure and stereochemistry. A LC-MS technique was employed for the identification of forskolin in crude extracts and in marketed formulations. A C18 column (150 x 4.6 mm, 5 pm) was used at ambient temperature. The mobile phase consisted of water (A) and acetonitrile (B). At a flow rate of 0.5 ml min the gradient elution was programmed to change from 50A/50B to 43A/57B in 10 min and to remain constant at 43A/57B for next 10 min. The detection wavelength was 210 nm, and the injection volume was 5 pi. Best results were obtained in positive electrospray ionization (ESI) mode, with ionization voltage set to 25 V, source voltage to 3.0 kV, and probe temperature to 350 °C [61]. 

The ionization mode most effective in ergot alkaloid analysis is positive electrospray ionization, which produces more intense protonated molecular ions than the deprotonated molecular ions that result from negative ionization, and this has become the preferred ionization method. When ergot alkaloids are ionized in positive electrospray mode the ions formed are predominantly the protonated molecular ions [M -i- H] -i- ions, with little evidence of adduct formation with ions of sodium, potassium, or ammonia, despite the ubiquitous presence of sodium in aqueous mobile phase solvents and the addition of comparatively high levels of ammonium salts. 

Kasprzyk-Hordem, B., R. M. Dinsdale, and A. J. Guwy. 2007. Multi-residue method for the determination of basic/neutral pharmaceuticals and illicit drugs in surface water by solid-phase extraction and ultra performance liquid chromatography-positive electrospray ionization tandem mass spectrometry. J. Chromatogr. A 1161 132—145. 

An LC—MS—MS method to determine cefaclor in human plasma. Plasma samples are treated by precipitation (PPT) or solid-phase extraction (SPE). The LC column is a C18 phase the detector is a triple quadmpole tandem mass spectrometer in positive electrospray ionization (ESI) mode. Quantitative measurements or the PPT method were possible down to 100 ng/ml. Intra- and interday standard deviations <12%. Accuracy >3% (relative error) for the whole hnear calibration range. Test time 3.2 min. In the case of the SPE method, the quantitation was as low as 2 ng/ml. Precision and accuracy were 7 and 3%, respectively. The method was successfully used in pharmacokinetic tests of a cefaclor sustained-release formulation. 

An LC-MS-MS method to study the pharmacokinetic behavior of adefovir, an antihepatitis B virus drug. Following protein precipitation the sample is analyzed on a C18 column, using a triple-quadrupole tandem mass spectrometer as detector in the positive electrospray ionization mode and PMPA as the internal standard. The method is hnear in the concentration range 0.25-100 ng/ml, with the lower hmit of quantification 0.25 ng/ml. The intra- and interday relative standard deviation over the entire concentration range is <5.7%. The accuracy determined at three concentrations is within 2.5% relative error. The method was successfully used in pharmacokinetic studies. 

After TMS derivatization, flavonoids are injected onto a nonpolar capillary column in the split or splitless modes, and separated with a lineal 30-90 min temperature program up to 320°C. MS detector with positive electrospray ionization (ESI) and a temperature source of up to 250°C is the most common detection system used for the identification of flavonoids in the selected-ion monitoring (SIM) mode (Table 3.6). The molecular ion, [M-l-H], and fragment ions formed by the loss of CH3 or CO, as well as retro-Diels-Alder (RDA) reaction are typically used for identiflcation. 

In positive electrospray ionization, the ions most commonly formed by the electrolysis current are ferrous ions from the oxidation of the steel tip. For more electrochemically inert contact materials, the oxidation products can be hydrogen ions and hydrogen peroxide or oxygen. In negative ESI, the reaction at the contact must be reduction and since the contact material cannot be further reduced, something in the solution must be reduced. This reduction can sometimes lead to a significant change in the composition of the sprayed solution. 

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