Metabolism studies sensitivity

Johnston, M.C., Sulik, K.K. and Dudley, K.H. (1979). Genetic and metabolic studies of the differential sensitivity of A/J and C57BL/6J mice to phenytoin ( Dilantin )-induced cleft lip. Teratology 19 33 A. 

Lord et al. analyzed a mixture of steroids by CEC-ESI/MS and interfaced externally tapered CEC columns in both sheathless and sheath-flow arrangement. Sensitivity was found 20-fold higher in the sheathless configuration. The same conclusion was drawn by Warriner et ah, who evaluated CEC-nanospray/MS vs. CEC-microspray/MS with an ion trap using five corticosteroids. Cahours et al. used CEC-ESI/MS for a drug metabolism study and obtained a simultaneous baseline separation of flunitrazepam and its major metabolites. For CEC-ESI/MS coupling, the commercially available packed-CEC column was connected... 

Applications of High-Sensitivity Mass Spectrometry and Radioactivity Detection Techniques in Drug Metabolism Studies... 

High-sensitivity techniques for the quantitation and characterization of circulating metabolites following administration of radiolabeled compounds are of critical importance to understand the safety and efficacy profiles of novel drug candidates. AMS is one of the most sensitive techniques for the detection of radiolabeled components. However, the high cost and slow throughput of AMS analysis preclude the routine use of the techniques for metabolism studies. 

Nassar, A. E., and Lee, D. Y. (2007b). Novel radio-HPLC detector for sensitive metabolite profiling and structural elucidation in support of drug metabolism studies. Drug Metab. Rev. 39(Suppl. 1) 73. 

In rodent metabolism studies both parent compound and metabolite were detected in feces and metabolites were detected in urine using GC/LRMS. HRGC/LRMS has also been used successfully in determination of CDDs in rat feces (Abraham et al. 1989a). Adequate comparisons of sensitivity, accuracy, and precision cannot be made because of the lack of these data for several methods and the differences in the media and analytes for the available data. 

Because photomultiplier tubes can only detect events which occur on or near the surface of the scintillator column exposed to the tubes, the greater the surface to volume ratio, the more efficiently events will be detected. The literature contains a number of suggestions in which the simple U-tube is modified into coils and spirals which present larger surfaces per unit of volume to the photomultiplier tubes (3j. While this does increase sensitivity, a practical limit to minimum required sensitivity is set in most metabolism studies by the fact that we must separate enough compound to carry through identification studies. Since we have the option of selecting the specific activity of our original l c-compound, we have found the U-tubes described entirely adequate. 

Pharmacological and metabolic studies on cannabinoids (Fig. 1) have suffered from a lack of knowledge of their physico-chemical properties and the insensitivity of assays of A -tetrahydrocannabinol 1, and its metabolites in biological fluids. Unambiguous, sensitive, specific and accurate quantification is required for forensic toxicology and pharmacokinetic studies which can be correlated with the time course of the psychoactive effects (2). 

A number of studies have investigated the bioconversion, fate, and elimination of CR in various animal species (French et al, 1983 Fumival et al, 1983 Balfour, 1978 Harrison et al, 1978). Human metabolic studies on CR have not been performed due to the high degree of sensitivity of human tissues to CR. The maximum tolerated dosage is far too low to allow for detection in metabohc studies (Olajos,... 

Thermal ionization mass spectrometry has been used extensively in the geological nuclear and analytical sciences for stable isotope measurements A new technique resonance ionization mass spectrometry offers a comprehensive approach to sensitive and selective elemental and isotopic analysis Recent developments in thermal and resonance ionization mass spectrometry are reviewed) and specific applications of the technology to zinc and calcium metabolism studies and to trace element analysis of foodstuffs are summarized ... 

For a number of reasons, e.g., reduced sample consumption and enhanced sensitivity due to a lower solvent load to the ESI interface, the use of packedcapillary columns [9, 16-18] has been promoted for metabolism studies. These columns are applied in combination with a short trapping precolumn to enable larger injection volumes without compromising the performance of the analytical column. 

The most definitive assessment of the metal composition of metalloproteins comes from the application of element-specific detection methods. CE-ICP-MS provides information not only about the type and quantity of individual metals bound to the proteins but also about the isotopes of each element as well [11,12]. Elemental speciation has become increasingly important to the areas of toxicology and environmental chemistry. Such analytical capability also opens up important possibilities for trace element metabolism studies. Figure 1 depicts the separation of rabbit liver metallothionein containing zinc, copper, and cadmium (the predominant metal) using CE-ICP-MS with a high-sensitivity, direct injection nebulizer (DIN) interface. UV detection (200 nm) was used to monitor the efficiency of the CE separation of the protein isoforms (MT-1 and MT-2), whereas ICP-MS detection made it possible to detect and quantify specific zinc, copper (not shown), and cadmium isotopes associated with the individual isoform peaks. 

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