Drug Metabolism in Drug Design and Development Basic Concepts and Practice

As the drug enters Phase I clinical trials the drug metabolism efforts focus on identifying both circulating and excreted metabo ...

11.4 TECHNIQUES FOR IMPROVING METABOLITE DETECTION AND IDENTIFICATION 11.4.1 Chemical Derivatization Chemical derivatization use ...

(also see later in Section 11.7.2) alone is a challenging task because these analytes exhibit the samem/zfor their protonated or ...

ring in RTCOOH. Similarly, the detection of doublet peaks with anm/z difference of 2 Th at 113 and 115 Th in the mass spectrum s ...

of NS bond. Based on these data, the major metabolite M11 was proposed as dihydroziprasidone (Scheme 11.3). 11.4.4 Accurate Mas ...

mass resolution of 10^4 –10^5 with a mass accuracy better than 2 ppm. During the past decade, the application of the sector inst ...

results in mass spectral peak intensities that more accurately reflect relative amounts of material as compared to traditional o ...

responses varied by a 21-fold range, while in the NSI MS (Fig. 11.4b) the responses varied only by 2.2-fold across all compounds ...

integration of knowledge-based metabolic prediction with data-dependent LC/MSn to study the biotransformation of indinavir (Anar ...

defects lie outside of the window specified for drug-related ions. With a mass defect window set approximately50 mDa from that ...

identified in the ion chromatogram (Fig. 11.5b). In addition, mass spectra of the metabolite peaks were greatly simplified after ...

deriving detailed structural information once preliminary data on the nature of the metabolic change is available from LC/MS. St ...

in-source fragmentation. This may lead to an overestimation of the aglycone concentration if the chromatographic separation betw ...

from thermal energy activation in the vaporizer of the APCI and APPI sources. The most prominent fragment ion (m/z 313) resulted ...

solvents and rapidly underwent Cope elimination leading to the corresponding hydroxylamine metabolite M-5 and acrylic acid (Sche ...

11.8 DETECTION AND CHARACTERIZATION OF REACTIVE METABOLITES AND INTERMEDIATES Bioactivation is a long standing issue for drug de ...

11.8.2 Screening for Glutathione Conjugates Glutathione (GSH, g-glutamylcysteinylglycine) is present virtually in all mammalian ...

2005). An equimolar ratio of glutathione and^13 C 2 =^15 N-labeled glutathione (stable-isotope label in glycine residue) was app ...

facilitate high throughput screening for reactive metabolites of molecules in the discovery stage programs. Recently, Castro-Per ...

Different classes of GSH-conjugates appear to behave differently upon collision-activated dissociation; not all afford a neutral ...