Liquid chromatography-mass spectrometry atmospheric-pressure ionization techniques

See also Chemometrics and Statistics Optimization Strategies. Chromatography Overview Principies. Derivatization of Analytes. Extraction Soivent Extraction Principies Solid-Phase Extraction. Forensic Sciences Systematic Drug Identification. Gas Chromatography Mass Spectrometry. Hormones Steroids. Liquid Chromatography Liquid Chromatography-Mass Spectrometry. Mass Spectrometry Atmospheric Pressure Ionization Techniques Forensic Applications. 

Puig et al. [450] determined ng/1 levels of priority methyl-, nitro-, and chloro-phenols in river water samples by an automated on-line SPE technique, followed by liquid chromatography-mass spectrometry (LC-MS) using atmospheric pressure chemical ionization (APCI) and ion spray interfaces. 

The number of detectors that are sensitive and selective enough to be applied online with LC is limited because the solvents used are not compatible, as in the case of immunochemical detection after reversed- or normal-phase LC. The technology of coupling is still under development and not yet available in a large number of laboratories not specialized in techniques such as LC-MS. Therefore, LC separations are frequently followed by offline detection. Confirmatory analysis of suspected liquid chromatographic peaks can be made possible by coupling liquid chromatography with mass spectrometry. Atmospheric-pressure chemical ionization LC-MS has been employed for the identification of six steroid hormones in bovine tissues (448). 

They are still the workhorses of coupled mass spectrometric applications, as they are relatively simple to run and service, relatively inexpensive (for a mass spectrometer), and provide unit mass resolution and scanning speeds up to approximately 10,000 amu/s. This even allows for simultaneous scan/ selected ion monitoring (SIM) operation, in which one part of the data acquisition time is used to scan an entire spectrum, whereas the other part is used to record the intensities of selected ions, thus providing both qualitative information and sensitive quantitation. They are thus suitable for many GC-MS and liquid chromatography-mass spectrometry (LC-MS) applications. In contrast to GC-MS with electron impact (El) ionization, however, LC-MS provides only limited structural information as a consequence of the soft ionization techniques commonly used with LC-MS instruments [electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI)]. Because of this limitation, other types of mass spectrometers are increasingly gaining in importance for LC-MS. 

As an instrumental approach to conventional electrophoresis, capillary electrophoresis offers the capability of on-line detection, micropreparative operation and automation (6,8,45-47). In addition, the in tandem connection of capillary electrophoresis to other spectroscopy techniques, such as mass spectrometry, provides high information content on many components of the simple or complex peptide under study. For example, it has been possible to separate and characterize various dynorphins by capillary electrophoresis-mass spectrometry (33). Therefore, the combination of CE-mass spectrometry (CE-MS) provides a valuable analytical tool useful for the fast identification and structural characterization of peptides. Recently, it has been demonstrated that the use of atmospheric pressure ionization using Ion Spray Liquid Chromatography/ Mass Spectrometry is well suited for CE/MS (48). This approach to CE/MS provides a very effective and straightforward method which allow the feasibility of obtaining CE/MS data for peptides from actual biological extracts, i.e., analysis of neuropeptides from equine cerebral spinal fluid (33). 

A variety of MS formats are widely accepted and applied in the pharmaceutical industry. The specific MS application is often defined by the sample introduction technique. The pharmaceutical applications highlighted in this article feature two types of sample introduction techniques dynamic and static. Dynamic sample introduction involves the use of high-performance liquid chromatography (HPLC) on-line with MS. The resulting liquid chromatography/mass spectrometry (LC/MS) format provides unique and enabling capabilities for pharmaceutical analysis. The electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) modes are the most widely used. Static sample introduction techniques primarily use matrix-assisted laser desorption/ionization (MALDI). ... 

Many approaches have been used to form ions, both in high-vacuum and near-atmospheric pressure conditions. Electron ionization (El) and chemical ionization (Cl) are ionization techniques used when gas phase molecules can be introduced directly into the analyzer from a gas chromatograph. In other analyses, such as high-performance liquid chromatography-mass spectrometry (HPLC-MS),... 

It has become painfully obvious that most of the excellent approaches and techniques that have been developed for use in liquid chromatography are not applicable to liquid chromatography/mass spectrometry (LC/MS) with atmospheric pressure ionization. Chapter 5 described the reagents and the range of mobile-phase compositions that are compatible with electrospray and atmospheric pressure chemical ionization (APCI), and these are limited to volatile components that do not cause significant ion suppression. Certain problems that are not significant with standard LC separations become difficult to deal with because of the limitations placed on the mobile phase by atmospheric pressure ionization (API) LC/MS. 

The coupling of liquid chromatography (LC) with mass spectrometry (MS) has undergone much evolution since its initial inception [1,2], Atmospheric pressure ionization techniques such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) opened the door for the ionization and analysis of nonvolatile or thermally labile analytes. This technique revolutionized drug discovery and development allowing for dramatic improvements in sensitivity, selectivity, and speed. This area continues to grow, and significant advances have been and continue to be achieved in all three areas [3-5],... 

T Wachs, JC Conboy, F Garcia, JD Henion. Liquid chromatography-mass spectrometry and related techniques via atmospheric pressure ionization. J Chromatogr Sci 29 357, 1991. 

Kampo medicines in which A.fangchi root or A. manshuriensis stem may be misused [492], Moreover, LC-PDA and LC-EIMS detection methods both were effective in distinguishing AAI (5) and AAII (5) peaks by their spectra. Very recently, we have reported the extensive analysis of aristolochic acids and aristolactams in the various Chinese medicinal plants and crude drugs using different techniques. A method has been developed using reversed phase liquid chromatography coupled with atmospheric pressure chemical ionization (APCI) tandem mass spectrometry under the positive ion detection mode [LC/(+)APCI/MS/MS] to determine the amount of AA-1(5) in Xinxin, a traditional Chinese medicine that originate from nine Asarum species... 

Liquid chromatography-mass spectrometry The initial attempts to couple LC with MS lacked important attributes for trace analysis sensitivity, robustness, and reliable quantitation. Moreover, the cost of the early LC-MS instruments was prohibitive for most laboratories. The revolutionary introduction of atmospheric pressure ionization (API) techniques, mainly electrospray (ESI) and atmospheric pressure chemical ionization (APCI), resulted in greater applicability of LC-MS and manufacture of more reliable, affordable, and user-friendly instruments. Thus, LC-MS is now becoming an indispensable part of the analytical strategy in many routine laboratories, enabling direct, selective, and sensitive multiclass, multiresidue analysis of more polar, low volatile, and/or thermolabile pesticides, such as carbamates, phenylureas, sulfonylureas, imidazoles, triazoles, imidazolinones, chlorophenoxy acids, and many others. 

The most commonly used analytical technique for sugars is HPLC with a refractive index detector (RID). Although the HPLC-RID method is simple, the RID lacks sensitivity and selectivity. Therefore, UV and fluorescence detection is frequently used, coupled with pre- or postcolumn derivatization, for analysis with higher sensitivity. Liquid chromatography-mass spectrometry (LC-MS) using electrospray ionization also requires pre- or postcolumn derivatization. LC-MS using atmospheric pressure chemical ionization does... 

See also Atomic Mass Spectrometry Inductively Coupled Plasma Laser Microprobe. Gas Chromatography Mass Spectrometry. Liquid Chromatography Liquid Chromatography-Mass Spectrometry. Mass Spectrometry Ionization Methods Overview Atmospheric Pressure Ionization Techniques Electrospray Liquid Secondary Ion Mass Spectrometry Matrix-Assisted Laser Desorption/ionization. Surface Analysis Secondary Ion Mass Spectrometry of Polymers Laser Ionization. 

Traditionally, products and adsorbates had to be volatile enough so that they could be carried from the cell into the mass spectrometer, either by headspace sampling, or, more commonly for near-simultaneous analysis (referred to as differential electrochemical mass spectrometry), across a nanoporous, gas-permeable membrane (e.g., Teflon) supported at the tip of a microcapillary placed close to the electrode. Alternatively, a Pt-coated membrane electrode can be used. But the advent of the so-called soft atmospheric pressure desorption/ionization techniques associated with liquid chromatography-mass spectrometry has allowed the sampling of the solvent and involatile solutes directly. The spectra are more... 

Leinonen, A. Kuuranne, T. Kostiainen, R. Liquid chromatography/mass spectrometry in anabolic steroid analysis—optimization and comparison of three ionization techniques Electrospray ionization, atmospheric pressure chemical ionization and atmospheric pressure photoionization. J. Mass Spectrom. 2002, 37 (7), 693-698. 

A wide variety of liquid chromatography-mass spectrometry (LC-MS) techniques have been reported for retinoid analysis including direct liquid introduction with Cl (281,282,299-301), particle beam (302-304), thermospray (305-307), electrospray (308,309), and atmospheric pressure chemical ionization (APCI) (310). Because many of the early LC-MS applications to retinoids carried out hydrolysis of retinyl esters and then derivatization of retinoic acid and related retinoids, Wyss (141) predicted in a review of retinoid analysis that derivatization of retinoids would be necessary for all LC-MS techniques, even the anticipated application of atmospheric pressure chemical ionization (APCI). Recently, LC-MS analyses of retinoids have been carried out using APCI (310) and electrospray (308,309), and highly sensitive LC-MS analyses of retinoic acid and retinyl esters were achieved without hydrolysis or derivatization. 

Electrospmy ionization (ESI) is the most prominent technique among the group of atmospheric pressure ionization (API) methods and the leading method of choice for liquid chromatography-mass spectrometry coupling (LC-MS, Chap. 14) [1-4], In fact, ESI and MALDI (Chap. 11) have provided the means for extending the analytical procedures of MS into the fields of biology and the biomedical sciences, and currently, they are the most frequently employed ionization methods in MS [1,2,4-9]. 

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. 

Thomas etal. [72] used pyrolysis gas chromatography-mass spectrometry as a fast economic screening technique for polyaromatic hydrocarbons. Thomas used reverse-phase liquid chromatography with atmospheric pressure chemical ionization mass spectrometry/mass spectrometry for the determination of polycyclic aromatic sulphur heterocycles in sediments. 

The application of liquid chromatography-atmospheric pressure ionization-mass spectrometry in water analysis has been previously reviewed. The application of this technique for the analysis of synthetic dyes was also discussed [118]. 

In atmospheric pressure ionization sources (API) the ions are first formed at atmospheric pressure and then transferred into the vacuum. In addition, some API sources are capable of ionizing neutral molecules in solution or in the gas phase prior to ion transfer to the mass spectrometer. Because no liquid is introduced into the mass spectrometer these sources are particularly attractive for the coupling of liquid chromatography with mass spectrometry. Pneumatically assisted electrospray (ESI), atmospheric pressure chemical ionization (APCI) or atmospheric pressure photoionization (APPI) are the most widely used techniques. 

Currently, high-performance liquid chromatography (HPLC) combined with atmospheric pressure ionization (API) triple-quadrupole mass spectrometry (MS) is the predominate quantitative technique used in modem pharmaceutical bioanalysis. The key technological achievement in API-MS was the efficient ionization in a liquid stream and transference of ions from atmosphere to vacuum. Of the API approaches developed, electrospray ionization (ESI) is the most commonly used. ESI provides an efficient means of soft ionization amenable to most molecules encountered in a dmg discovery setting. An alternative soft ionization approach is the use of desorption ionization (DI) techniques. The major distinguishing feature of DI techniques is that ions are typically produced from dried samples. 

Brewer E, Henion J (1998) Atmospheric Pressure Ionization LC/MS/MS Techniques for Drug Disposition Studies. Journal of Pharmaceutical Sciences 87(4) 395—402 Kollroser M, Schober C (2002) Simultaneous analysis of flu-nitrazepam and its major metabolites in human plasma by high performance liquid chromatography tandem mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis 28 1173-1182... 

The need for an ionization source that provided both softer ionization, i.e., less fragmentation of the molecular ion, and a convenient interface with liquid chromatography (at ambient pressure) to mass spectrometry (at high vacuum) helped spur the creation of atmospheric pressure ionization. Two techniques fall under the heading of API, electrospray and atmospheric pressure chemical ionization (APCI), and the technical aspects of each are discussed individually. However, many of the fundamental principals that describe these ionization mechanisms can be applied to both electrospray and APCI sources. 

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