Metabolite identification quantification

Pharmacology Drug and metabolite identification/quantification (pharmacokinetics, pharmacodyn nics, pharmacogenetics)... 

Khachik, F. et al., Identification, quantification, an relative concentrations of carotenoids and their serum metabolites in human milk and serum, Anal. Chem., 69, 1873, 1997. 

Zhang, N., Fountain, S. T., Bi, H., and Rossi, D. T. (2000). Quantification and rapid metabolite identification in drug discovery using API time-of-flight LC/MS. Anal. Chem. 72 800-806. 

Most analyses require several unit operations, namely separation of the poison from the biological material, isolation and purification of the toxic substance and its metabolites, identification, confirmation of identity, and quantification. The most useful methods are those which combine two or more of these unit... 

A relatively new and powerful tool in metabolite identification is the (J-LIT instrument. In this triple-quadrapole instmment, the third quadrupole can be apphed as a scanning quadmpole, but also as a linear ion trap (Ch. 2.4.2). Potential and additional features of a Q-LIT in metabolite identification have been discussed by various groups [44-45]. The advantages of triple-quadrupole MS-MS spectra at ion-trap sensitivity as well as the enhanced sensitivity and speed in DDA experiments with the (J-LIT was demonstrated for the collagenase inhibitor trocade [44]. Various enhanced scan functions of the Q-LlT were applied in the identification of 6-aminobutylphthalide metabolites in rat brains, using microdialysis and LC-MS-MS [45]. Simultaneous quantification of a parent compound and screening for its... 

Automated, rapid, high-throughput global analysis with minimal sample preparation, used for sample classification Limited ability for metabolite identification and quantification except for NMR... 

The potential of electrochemical detection (ECD) techniques for metabolite generation, detection, and quantification [283] should not be underestimated because the technique is especially useful for reactive metabolites [284,285], ECD can be used as standalone or as a parallel or sequential method with LC-MS systems. Online ECD techniques and their utility in metabolite identification have been recently reviewed by Gamache et al. [286], Most of the documented applications involve the use of the electrochemical cell for oxidizing an NCE to reactive metabolites and trapping and detecting them by online LC-MS and LC-MS/MS techniques. 

Leclercq, L. et al., Which human metabolites have we MIST Retrospective analysis, practical aspects, and perspectives for metabolite identification and quantification in pharmaceutical development, Chem. Res. Toxicol., 22(2), 280, 2009. 

The use of radiolabeled drugs is not only crucial for the quantification of unknown metabolites but has also long played a critical role in metabolite identification studies. The utility of radiolabeled substrates inelude (1) their use as tracers of drug-related components during sample elean-up, eoneentra-tion, profiling, and isolation from complex biological matrixes and (2) facilitation of LC-MS/MS detection of radiolabeled metabolites based on their HPLC retention times, peak shapes, and in some cases, isotopic ratios. 

A prerequisite for detection, identification, and quantification of any species by MS is that all analytes must be converted into gas-phase ions before they enter the mass analyzer. API techniques are most widely used for metabolite identification, mainly due to their ability to couple to liquid chromatography and generate intact gas-phase molecular ions at very high sensitivity (Rossi, 2002 Voyksner, 1997). 

Schrodei H.Er. Separation, Identification, Quantification of Surfactants, their Metabolites, in Waste Water, Surface Water, Drinking Water hy LC-TSP-MS, FIA-TSP-MS, MS-MS, in Applications of LC-MS in Environmental Chemistry, ed. Barcelo, D., Elsevier, Amsterdam 1996, p. 263. 

In LC/MS metabolite profiling and identification analysis, other liquid chromatographic detection formats, including UV, radiodetection, and NMR, are often employed to facilitate metabolite detection, quantification, or structural characterization. These liquid chromatographic detection formats provide high analytical values that are complementary to mass spectrometry and critical to accomplishing objectives of drug metabolism studies (Zhu et al., 2009). 

In this context, NMR spectroscopy has shown some important advantages in respect to the other analytical techniques, which can be summarized by ease of quantification, straightforward metabolite identification, and ability to determine unexpected metabolites [8]. Indeed, NMR analysis of a sample allows the simultaneous detection of low molecular weight metabolites present in a solution at a concentration beyond 10 M. 

A knowledge of the metabolic fate of a particular drug, both in terms of the identification and quantification of the metabolites, is necessary not only to ensure that its use will not cause more problems than the medical condition it is designed to alleviate but, from the drug company s perspective, to facilitate the design of more effective drugs. 

Absorption, Distribution, Metabolism, and Excretion. There are no data available on the absorption, distribution, metabolism, or excretion of diisopropyl methylphosphonate in humans. Limited animal data suggest that diisopropyl methylphosphonate is absorbed following oral and dermal exposure. Fat tissues do not appear to concentrate diisopropyl methylphosphonate or its metabolites to any significant extent. Nearly complete metabolism of diisopropyl methylphosphonate can be inferred based on the identification and quantification of its urinary metabolites however, at high doses the metabolism of diisopropyl methylphosphonate appears to be saturated. Animal studies have indicated that the urine is the principal excretory route for removal of diisopropyl methylphosphonate after oral and dermal administration. Because in most of the animal toxicity studies administration of diisopropyl methylphosphonate is in food, a pharmacokinetic study with the compound in food would be especially useful. It could help determine if the metabolism of diisopropyl methylphosphonate becomes saturated when given in the diet and if the levels of saturation are similar to those that result in significant adverse effects. 

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