High throughput liquid chromatography/mass spectrometric analyses using a novel multiplexed electrospray interface

Biasi, V. de; Haskins, N. J.; Organ, Andrew J.; Bateman, Robert; Giles, Kevin; Jarvis, S.

doi:10.1002/(sici)1097-0231(19990630)13:12<1165::aid-rcm638>3.0.co;2-4

Cited by 148 publications

(115 citation statements)

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“…In order to increase sample throughput while maintaining high-quality analytical data, groups have begun to perform separations in parallel [59][60][61][62][63]. Numerous groups have independently developed parallel sample introduction techniques, although the MUX ion source from Micromass/Waters is the only one commercially available.…”

Section: Parallel Analysis and Parallel Purificationmentioning

confidence: 99%

“…By performing analyses in parallel, chromatographic integrity can be maintained while effectively addressing sample throughput. Di Biasi et al [59] and Wang et al [60] presented novel ion source interfaces enabling four to eight samples to be processed in parallel, thereby increasing the sample analysis throughput dramatically over conventional, serial-based LC/MS analyses. Commercially available parallel spray interfaces consist of a multiple spray head assembly and a blocking device (e.g., rotating plate), enabling individual sprayers to be sampled at specific and defined time intervals.…”

Section: Parallel Analysis and Parallel Purificationmentioning

confidence: 99%

See 1 more Smart Citation

The Expanding Role of HPLC in Drug Discovery

Kassel

2006

HPLC for Pharmaceutical Scientists

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Section: Parallel Analysis and Parallel Purificationmentioning

confidence: 99%

Section: Parallel Analysis and Parallel Purificationmentioning

confidence: 99%

The Expanding Role of HPLC in Drug Discovery

Kassel

2006

HPLC for Pharmaceutical Scientists

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“…5). 162 In addition, multiple sprayers on an ESI interface are also available, and can analyze 96 samples in 1 h. 163 The progress in combinatorial chemistry and the growth in the chemical library size have also influenced the expansion of a high-throughput screening system. The common robotics highthroughput screening system can successively measure the pharmacological activities of a large chemical library, such as a receptor agonist or antagonist activity by spectroscopic detection using a plate reader.…”

Section: ·1 High-throughput Analysismentioning

confidence: 99%

Biomedical and Biological Mass Spectrometry

Mano

Goto

2003

ANAL. SCI.

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By the end of the 20th century, mass spectrometry (MS) had evolved drastically as a major analytical tool in biomedical and biological research. Recent mass spectrometers, designed for ease of handling, came into wide use in the 1990s. Soft ionization methods, which were made practical in the second half of the 1980s, allowed for the sensitive analysis of nonvolatile and thermolabile compounds by MS. Electrospray ionization (ESI) 1,2 and matrix-assisted laser desorption ionization (MALDI) 3 methods, made it possible to ionize large biomolecules and to transfer them to the gas phase, thereby becoming a valuable tool in both protein and peptide analysis [4][5][6] and in the study of drugs and their metabolites [7][8][9][10][11][12] in the human body. Many reviews of MS have recently been published, [13][14][15][16][17][18][19] and in particular, the number of reviews describing biochemical, biological, and biomedical MS have increased dramatically over the last ten years. Initially, there were many commentary reviews on new techniques, such as soft ionization methods and mass analyzers, 13-15 and more recently, review articles have focused on the biological and biomedical applications of MS. 18-21 Above all, two major fields, drug discovery and proteomics, have made marked advances based on MS.Articles in the MEDLINE database were searched, and the results are illustrated in Fig. 1 and Table 1. Over the last 15 years, a total of 79220 MS articles were placed in the database, with a 2.5-fold increase from 1987 to 1999. The number of articles using fast atom bombardment (FAB) as an ionization method remained almost constant during this period. This ionization method is a practical soft ionization procedure, which was applied to the analysis of peptides [22][23][24][25][26][27][28][29][30][31] and endogenous biological substances [32][33][34][35] in the 1980s. Atmospheric pressure chemical ionization (APCI) is a suitable method 36 for the ionization of middle or weakly polar low-molecular-weight molecules, and can be easily coupled to conventional highperformance liquid chromatography (HPLC), used at a flow rate of around 1 mL/min. [37][38][39][40][41][42][43][44][45][46][47][48] However, the number of articles concerning APCI have increased slowly, because most drugs developed recently contain polar groups which can be ionized without difficulty by the ESI technique. Japan This review focuses on biological and biomedical mass spectrometry, and covers a selection of publications in this area included in the MEDLINE database for the period 1987 -2001. Over the last 15 years, biological and biomedical mass spectrometry has progressed out of all recognition. The development of soft ionization methods, such as electrospray ionization and matrix-assisted laser desorption ionization, has mainly contributed to the remarkable progress, because they can easily produce gas-phase ions of large, polar, and thermally labile biomolecules, such as proteins, peptides, nucleic acids and others. The innovations of ionization meth...

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“…De Biasi et al 46) have described the use of four HPLC columns in parallel coupled to one ESI-TOF instrument. The MS was fitted with a four-channel multiplex ESI source, in which each of the four liquid streams is sampled for 0.1 seconds, resulting in the production of individual mass spectra synchronized to each HPLC column.…”

Section: )mentioning

confidence: 99%

Current Developments in LC-MS for Pharmaceutical Analysis

Lim

Lord

2002

Biological & Pharmaceutical Bulletin

151

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Liquid chromatography-mass spectrometry (LC-MS) is an analytical technique that couples high resolution chromatographic separation with sensitive and specific mass spectrometric detection. This includes high performance liquid chromatography (HPLC)-MS, capillary electrophoresis (CE)-MS and more recently capillary electrochromatography (CEC)-MS. The technique is still fast developing, particularly in the mass spectrometry area, with vastly improved sensitivity and resolution. It is probably the most powerful technique currently available for pharmaceutical analysis.This review is intended as a discussion on the current developments of LC-MS in pharmaceutical analysis rather than a review of literature alone. Various LC-MS techniques will be described briefly and the advantages and disadvantages of each will be discussed. DEVELOPMENTS IN LC-MS Brief History of LC-MSThe last twenty years has seen a dramatic increase in the capabilities of MS. At the beginning of this period the invention of fast atom bombardment (FAB), by Barber et al. in 1981, 1) enabled easier analysis of involatile and thermally unstable molecules, especially those of biological interest. It may be argued that this technique acted as a catalyst for the development of other ionization techniques, such as matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI), applicable to such molecules.The combination of liquid chromatographic techniques with MS has been an important development. Early interfaces were concerned with coping with the potential of 1 l/min vapour in the MS ionisation source vacuum that would be generated by eluent from typical analytical columns flowing at 1 ml/min. This was achieved by evaporating solvent on a heated moving belt, 2,3) or the use of very low flows, such as direct liquid introduction 4,5) and continuousflow FAB (CF-FAB).6) Thermospray 7) and particle beam 8) interfaces were improved methods during the 1980s.Atmospheric Pressure Ionization (ESI and APCI) Over the last decade, ESI and atmospheric pressure chemical ionization (APCI), have become the dominant techniques superseding thermospray etc. and are likely to remain so for the foreseeable future being inherently the most suitable for analytes in solution presented to the MS. ESI was originally proposed by Dole,9) who suggested using charged droplets as a source of ions for MS and Fenn 10) pioneered its development as an ionization source for MS, leading to the first commercially available instrument in 1989.In essence, the electrospray process involves producing a fine spray of ionized droplets from the outlet of a capillary carrying a liquid stream, which may be eluent from HPLC, CE, CEC or direct infusion of sample solution. This is achieved by applying a high voltage (typically 3-5 kV) to the outlet of the capillary at the spray tip, which creates a high electric potential and causes the production of a fine mist of droplets. This occurs at atmospheric pressure, hence the term atmospheric pressure ionization (API), is used. Thi...

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High throughput liquid chromatography/mass spectrometric analyses using a novel multiplexed electrospray interface

Cited by 148 publications

References 2 publications

The Expanding Role of HPLC in Drug Discovery

The Expanding Role of HPLC in Drug Discovery

Biomedical and Biological Mass Spectrometry

Current Developments in LC-MS for Pharmaceutical Analysis

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