Liquid chromatography-mass method development

A liquid chromatography-mass spectrometry (LC-MS) method that can quantitatively analyze urinar y normal and modified nucleosides in less than 30 min with a good resolution and sufficient sensitivity has been developed. Nineteen kinds of normal and modified nucleosides were determined in urine samples from 10 healthy persons and 18 breast cancer patients. Compounds were separ ated on a reverse phase Kromasil C18 column (2.1 mm I.D.) by isocratic elution mode using 20 mg/1 ammonium acetate - acetonitrile (97 3 % v/v) at 200 p.l/min. A higher sensitivity was obtained in positive atmospheric pressure chemical ionization mode APCI(-i-). 

The need to understand the fate of pesticides in the environment has necessitated the development of analytical methods for the determination of residues in environmental media. Adoption of methods utilizing instrumentation such as gas chro-matography/mass spectrometry (GC/MS), liquid chromatography/mass spectrometry (LC/MS), liquid chromatography/tandem mass spectrometry (LC/MS/MS), or enzyme-linked immunosorbent assay (ELISA) has allowed the detection of minute amounts of pesticides and their degradation products in environmental samples. Sample preparation techniques such as solid-phase extraction (SPE), accelerated solvent extraction (ASE), or solid-phase microextraction (SPME) have also been important in the development of more reliable and sensitive analytical methods. 

High performance liquid chromatography-mass spectrometric methods Nitin et al. [75] developed and validated a sensitive and selective liquid chromatography-tandem mass spectrometric method (LC MS MS) for the simultaneous estimation of bulaquine and its metabolites primaquine in monkey plasma. The mobile phase consisted of acetonitrile ammonium acetate buffer (20 mM, pH 6) (50 50, v/v) at a flow rate of 1 mL/min. The chromatographic separations were achieved on two Spheri cyano columns (5 pm, 30 cm x 4.6 mm), connected in... 

The year 2002 was an extraordinary year for liquid chromatography-mass spectrometry (LC/MS) practitioners. On October 9, 2002, the Royal Swedish Academy of Sciences annonnced their decision to award the Nobel Prize in Chemistry to John B. Fenn, Koichi Tanaka, and Kurt Wiithrich for their development of analytical methods for the identification and structnral analysis of biological macromolecnles. Fenn and Tanaka shared the prize for developing electrospray and soft-laser desorption, respectively. These soft-ionization techniqnes allow macromolecules to be ionized withont fragmentation. 

Pulsed ultrafiltration MS (PUF-MS) represents an inline high throughput affinity screening method with a variety of potential uses in the discovery and development of pharmaceuticals [22]. The in-line combination of solution-phase equilibration, ultrafiltration, and electrospray liquid chromatography mass spectrometry (LC-ESI-MS) facilitates the identification of high affinity target-specific... 

Crescenzi, C., A. Di Corcia, E. Guerriero, and R. Samperi (1997). Development of a multiresidue method for analyzing pesticide traces in water based on solid-phase extraction and electrospray liquid chromatography mass spectrometry. Environ. Sci. Technol., 31 479 188. 

Liquid chromatography/mass spectrometry (LC/MS)-based techniques provide unique capabilities for pharmaceutical analysis. LC/MS methods are applicable to a wide range of compounds of pharmaceutical interest, and they feature powerful analytical figures of merit (sensitivity, selectivity, speed of analysis, and cost-effectiveness). These analytical features have continually improved, resulting in easier-to-use and more reliable instruments. These developments coincided with the pharmaceutical industry s focus on describing the collective properties of novel compounds in a rapid, precise, and quantitative way. As a result, the predominant pharmaceutical sample type shifted from nontrace/pure samples to trace mixtures (i.e., protein digests, natural products, automated synthesis, bile, plasma, urine). The results of these developments have been sig-... 

Little JL, Wempe MF, Buchanan CM (2006) Liquid chromatography-mass spectrometry/mass spectrometry method development for drug metabolism studies examining lipid matrix ionization effects in plasma. J Chromatogr B 833 219-230... 

Chi C, Liang L, Padovani P et al. (2003) Development and validation of a liquid chromatography-mass spectrometric method for the determination of DPC 423, an antithrombotic agent, in rat and dog plasma. J Chromatogr B Analyt Technol Biomed Life Sci 783( 1) 163—172 Zimmer D, Muschalek V, Muller C (2000) Determination of met-rifonate enantiomers in blood and brain samples using liquid chromatography on a chiral stationary phase coupled to tandem mass spectrometry. Rapid Commun Mass Spec-trom 14(15) 1425-1432... 

Both variolin B and its 5-deoxy derivative 19 (Scheme 6.1 Part 2) have shown promise in pharmacokinetic and in vivo studies. These compounds have been shown to have long terminal half-lives and low normal cell toxicity, however the 5-deoxy derivative demonstrated better Cmax, plasma clearance and terminal plasma half-life.318,319 Both are effective against human lung carcinoma cell lines in nude mice.104 The deoxy-variolin B showed growth inhibitory activity against human leukemic cell lines.105 A standardised method for liquid chromatography-mass spectrometry (LC-MS)/MS analysis of plasma has been developed to monitor the results of the in vivo studies.320... 

The first liquid chromatography method introduced to determine ezetimibe and its metabolites was developed by Ezzet et al. [58], and the method was used to model the pharmacokinetics of ezetimibe in humans. The liquid chromatography-mass spectrometry (LC-MS) method was used to determine imchanged ezetimibe and total ezetimibe (imchanged ezetimibe together with ezetimibe glucoronide) in human plasma samples. 

Stokes, P. O Connor, G. Development of a liquid chromatography-mass spectrometry method for the high-accuracy determination of creatinine in serum. J. Chromatogr., B 2003, 794, 125-136. 

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