Metabolites in Safety Testing

This chapter summarizes the current thinking and practices in the pharmaceutical industry in support of metabolites in safety testing (MIST) related activities. It compares two of several options available for conducting absorption, distribution, metabolism, and excretion (ADME) studies using radiolabled materials. In the first option, radiolabeled studies are not scheduled until after the interpretation of human pharmacokinetics (PK) and metabolism in the first-in-human (FIH) studies, while in the second option, preclinical radiolabeled ADME studies are initiated before the completion of the FIH studies. The chapter discusses some of the liquid chromatography-mass spectrometry (LC-MS) methods available for detecting and characterizing metabolites. Bioanalytical assays, used for detection, characterization and exposure estimation of metabolites, are tiered into (i) metabolite profiling, (ii) standard free quantification/ response factor determination, (iii) qualified assays, and (vi) validated assays

High-resolution mass spectrometry method for the detection, characterization and quantitation of pharmaceuticals in water

The presence of pharmaceuticals in drinking water is an emerging environmental concern. In most environmental testing laboratories, LC-MS/MS assays based on selected reaction monitoring are used as part of a battery of tests used to assure water quality. Although LC-MS/MS continues to be the best tool for detecting pharmaceuticals in water, the combined use of hybrid high-resolution mass spectrometry (HRMS) and ultrahigh pressure liquid chromatography (UHPLC) is starting to become a practical tool to study emerging environmental contaminants. The hybrid LTQ-orbitrap mass spectrometer is suitable for integrated quantitative and qualitative bioanalysis because of the following reasons: (1) the ability to collect full-scan HRMS spectra with scan speeds suitable for UHPLC separations, (2) routine measurement of mass with less than 5 ppm mass accuracy, (3) high mass resolving power, and (4) ability to perform on-the-fly polarity switching in the linear ion trap (LTQ). In the present work, we provide data demonstrating the application of UHPLC-LTQ-orbitrap for the detection, characterization and quantification of pharmaceuticals and their metabolites in drinking water. Copyright © 2011 John Wiley & Sons, Ltd

PHYTOREMEDIATION POTENTIAL OF VETIVER GRASS [CHRYSOPOGON ZIZANIOIDES (L.)] FOR TETRACYCLINE

The presence of veterinary and human antibiotics in soil and surface water is an emerging environmental concern. The current study was aimed at evaluating the potential of using vetiver grass as a phytoremediation agent in removing Tetracycline (TC) from aqueous media. The study determined uptake, translocation, and transformation of TC in vetiver grass as function of initial antibiotic concentrations and exposure time. Vetiver plants were grown for 60 days in a greenhouse in TC contaminated hydroponic system. Preliminary results show that complete removal of tetracycline occurred within 40 days in all TC treatments. Initial concentrations of TC had significant effect (p \u3c 0.0001) on the kinetics of removal. Tetracycline was detected in the root as well as shoot tissues, confirming uptake and root-to-shoot translocation. Liquid-chromatography-tandem-mass-spectrometry analysis of plant tissue samples suggest presence of metabolites of TC in both root and shoot tissues of vetiver grass. The current data is encouraging and is expected to aid in developing a cost-effective, in-situ phytoremediation technique to remove TC group of antibiotics from wastewater