In vivo pharmacokinetic screening in cassette dosing experiments: the use of on-line prospekt® liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery

“…This practice, made possible by the extraordinary specificity of tandem MS detection, is seen as a way to maximize the utilization of expensive LC/MS/MS instrumentation and to minimize the number of animals used. Since the initial reporting of N-in-one dosing by Berman and co-workers in 1997 [1], several reports have appeared in the literature [2][3][4][5]. Interested readers are also referred to a seminal article by White and Manitpisitkul on the pharmacokinetic implications of CD [6].…”

Section: Background On Cassette Dosingmentioning

confidence: 99%

Results from a bench marking survey on cassette dosing practices in the pharmaceutical industry

Ackermann

2004

J. Am. Soc. Mass Spectrom.

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“…This characteristic permits in vivo pharmacokinetics screening in cassette dosing experiments, and the use of a fully automated system using a column switching technique can analyze between 320 to 960 samples per day per instrument in a 64-inone experiment. 170 With this method, 100 µL of a plasma mixture can be loaded (the 1:1 mixture of plasma and 0.1 mol/L acetic acid) directly onto the extraction cartridge with octadesylsilylated silica gel, and analyzed within 4.5 min of injection. When using cassette dosing approaches, the concern for drug-drug interactions, such as inhibition or competition of drug transporting pathways, is very important.…”

Section: ·2 Drug Metabolismmentioning

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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In vivo pharmacokinetic screening in cassette dosing experiments: the use of on-line prospekt® liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry technology in drug discovery

Cited by 82 publications

References 2 publications

An automated screening method for drugs and toxic compounds in human serum and urine using liquid chromatography–tandem mass spectrometry

An automated screening method for drugs and toxic compounds in human serum and urine using liquid chromatography–tandem mass spectrometry

Results from a bench marking survey on cassette dosing practices in the pharmaceutical industry

Biomedical and Biological Mass Spectrometry

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