Electrospray ionization mass spectrometry limitations

A sensitive, simple, and specific liquid chromatographic method coupled with electrospray ionization-mass spectrometry for the determination of donepezil in plasma was developed, and its pharmacokinetics in healthy, male, Chinese was studied [34]. Using loratadine as the IS, after extraction of the alkalized plasma by isopropyl alcohol-n-hexane (3 97, v/v), solutes are separated on a Cig column with a mobile phase of methanol-acetate buffer (pH 4.0) (80 20, v/v). Detection is performed with a TOF mass spectrometer equipped with an electrospray ionization source operated in the positive-ionization mode. Quantitation of donepezil is accomplished by computing the peak area ratio (donepezil [M + H](+) m/z 380-loratadine [M + H](+) mlz 383) and comparing them with the calibration curve (r = 0.9998). The linear calibration curve is obtained in the concentration range 0.1-15 ng/ml. The limit of quantitation is 0.1 ng/ml. The mean recovery of donepezil from human plasma is 99.4 6.3% (range 93.4-102.6%). The inter- and intra-day RSD is less than 15%. After an oral administration of 5 mg donepezil to 20 healthy Chinese volunteers, the main pharmacokinetic parameters of donepezil are as follow T(max), 3.10 0.55 h tV2j 65.7 12.8 h C(max), 10.1 2.02 ng/ml MRT,... 

A sensitive and rapid chromatographic procedure using a selective analytical detection method (electrospray ionization-mass spectrometry in SIM mode) in combination with a simple and efficient sample preparation step was presented for the determination of zaleplon in human plasma. The separation of the analyte, IS, and possible endogenous compounds are accomplished on a Phenomenex Lima 5-/rm C8(2) column (250 mm x 4.6 mm i.d.) with methanol-water (75 25, v/v) as the mobile phase. To optimize the mass detection of zaleplon, several parameters such as ionization mode, fragmentor voltage, m/z ratios of ions monitored, type of organic modifier, and eluent additive in the mobile phase are discussed. Each analysis takes less than 6 min. The calibration curve of zaleplon in the range of 0.1-60.0 ng/ml in plasma is linear with a correlation coefficient of >0.9992, and the detection limit (S/N = 3) is 0.1 ng/ml. The within- and between-day variations (RSD) in the zaleplon plasma analysis are less than 2.4% (n = 15) and 4.7% (n = 15), respectively. The application of this method is demonstrated for the analysis of zeleplon plasma samples [14]. 

Some reviews [5-7] have appeared on NCE-electrospray ionization-mass spectrometry (NCE-ESI-MS) discussing various factors responsible for detection. Recently, Zamfir [8] reviewed sheathless interfacing in NCE-ESI-MS in which the authors discussed several issues related to sheathless interfaces. Feustel et al. [9] attempted to couple mass spectrometry with microfluidic devices in 1994. Other developments in mass spectroscopy have been made by different workers. McGruer and Karger [10] successfully interfaced a microchip with an electrospray mass spectrometer and achieved detection limits lower than 6x 10-8 mole for myoglobin. Ramsey and Ramsey [11] developed electrospray from small channels etched on glass planar substrates and tested its successful application in an ion trap mass spectrometer for tetrabutylammonium iodide as model compound. Desai et al. [12] reported an electrospray microdevice with an integrated particle filter on silicon nitride. 

In the authors and several other OPCW-designa-ted laboratories, LC/MS is used as the initial screening procedure for water samples and aqueous extracts of matrices such as soil. This usually provides a tentative identihcation of polar analytes within half a day, on the basis of molecular mass, any fragment ions present, and retention time. A second analysis, under LC/MS/MS conditions, usually provides a firmer identihcation on the basis of a limited number of product ions, most of which result from simple neutral losses. With clean matrices, the initial screening may be performed even faster using how injection or infusion rather than LC (14). An example of the application of how injection with electrospray ionization/mass spectrometry (ESI/MS) in an OPCW prohciency test is provided by Hooijschuur et al. (21) The identihcation of the analytes is usually conhrmed by GC/MS (in most cases after derivatization) as the second technique. 

Infrared spectroscopy has been rarely used for PolyP characterization (Datema et al, 1977). Electrospray ionization mass spectrometry (ESI-MS) has been applied to the characterization of phosphates (P , PP , PolyP3, PolyPs and tricyclophosphate). The high selectivity of ESI-MS allowed the detection of these compounds without any pre-separation by ion chromatography or capillary electrophoresis. The limits of detection for ESI-MS were estimated to be in the range from approximately 1 to 10 ng ml-1 (Choi et al, 2000). 

The major drawback of CE is the poor concentration sensitivity due to the limited amount of sample volume that can be introduced into the capillary (nanoliters) and the low absorption path length if UV detection is used. However, in the combination of electrospray ionization-mass spectrometry (ESI-MS), lower limits of detection can be obtained. 

Regarding MS detection, authors described methods performed in positive ion mode using full scan and selected ion monitoring for PSP analysis [42,43], The pioneering PSP research in the area of electrospray ionization-mass spectrometry (ESl-MS) detection analysis has been conducted in the group of Quilliam et al. [46, 47]. In their studies, the authors used LC separation before pneumatically assisted ESI. Detection limits as low as 30 pg were obtained for positive ions of several STX analogs [46]. 

Improving the concentration detection limit is the goal of much analytical research and development. While miniaturization leading to lower mass detection limits is by no means trivial, it is at least conceptually obvious how to proceed. On the other hand, approaches to better concentration detection limits often require considerable creativity. In some cases, better detectors offer lower detection limits. Because properties of molecules differ, it is difficult to be globally accurate in a statement of relative merits of detectors, but experience shows that the inherent detection limits for compounds that are well suited for each detector are fluorescence < electrospray ionization mass spectrometry (ESI-MS) electrochemistry < optical absorbance. It is worth noting that low detection limit is correlated with the selectivity of the detector. In fact, in real samples of sufficient complexity (are there any real samples that are not complex ), Nagels has shown that detection limits correlate... 

In this study, the molecular mass and net charge of MUPs from six wild mice, taken from two separate populations, have been determined by electrospray ionization mass spectrometry and anion exchange chromatography respectively. This method of analysis uniquely identifies individual MUPs and has allowed an accurate determination of the number of different MUPs produced by these animals. In this limited sample, the number is much greater than previously observed in inbred mice. The results are discussed both in terms of the total number of MUPs characterised and the variation in heterogeneity between individual animals and populations. 

T. J. Thompson, F. Foret, P. Vouros, and B. L. Karger, Capillary eleclrophore-sis/electrospray ionization mass spectrometry improvement of protein detection limits using on-column transient isotachophoretic sample preconcentration. Anal. Chem. 65, 900-906(1993). 

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