High-throughput high-performance liquid chromatography/mass spectrometry for modern drug discovery

Kyranos, James N.; Cai, Hong; Wei, Darren; Goetzinger, Wolfgang

doi:10.1016/s0958-1669(00)00176-2

Cited by 68 publications

(33 citation statements)

References 48 publications

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“…HPLC plays an important role in determining the purity and identity of the compounds of interest. Most HPLC analyses use reversed-phase chromatography coupled to different detectors [1] or LC/MS [2][3][4][5][6][7]. Methods that are developed using C18 stationary phases have produced rugged and dependable separations.…”

Section: Introductionmentioning

confidence: 99%

Gradient elution of organic acids on a β-cyclodextrin column in the polar organic mode and its application to drug discovery

Simms¹,

Jeffries²,

Zhao³

et al. 2004

Journal of Chromatography A

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Section: Introductionmentioning

confidence: 99%

Gradient elution of organic acids on a β-cyclodextrin column in the polar organic mode and its application to drug discovery

Simms¹,

Jeffries²,

Zhao³

et al. 2004

Journal of Chromatography A

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“…In addition, "universal-like" HPLC gradients (e.g., 10% to 90% acetonitrile in water in 5 minutes) have been found to satisfy the separation requirements for the vast majority of combinatorial and parallel synthesis libraries. Fast HPLC/MS has been found to serve as good surrogate to conventional HPLC for assessing library quantity and purity [34][35][36][37]. Fast HPLC/MS is simple in concept.…”

Section: Hplc/ms Analysis To Support Compound Characterizationmentioning

confidence: 99%

The Expanding Role of HPLC in Drug Discovery

Kassel

2006

HPLC for Pharmaceutical Scientists

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“…57) High-throughput approaches to sample preparation coupled with LC-MS greatly improved the speed and sensitivity of analysis necessary for the accelerated drug discovery process.…”

Section: Fig 5 Hplc-esi-ms Separation Of Tamoxifen and Metabolites mentioning

confidence: 99%

Current Developments in LC-MS for Pharmaceutical Analysis

Lim

Lord

2002

Biological & Pharmaceutical Bulletin

149

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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 high-performance liquid chromatography/mass spectrometry for modern drug discovery

Cited by 68 publications

References 48 publications

Gradient elution of organic acids on a β-cyclodextrin column in the polar organic mode and its application to drug discovery

Gradient elution of organic acids on a β-cyclodextrin column in the polar organic mode and its application to drug discovery

The Expanding Role of HPLC in Drug Discovery

Current Developments in LC-MS for Pharmaceutical Analysis

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