Sensitivity of INADEQUATE

From Ref. 6, reproduced by permission of the Royal Society of Chemistry. 

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The COSY, TOeSY, HETCOR. and HMQC ex periments are great aids in interpreting proton and C spectra. However, the INADEQUATE experiment is perhaps the definitive 2D NMR technique. This experiment is based on spin-spin coupling between directly bonded pairs of nuclei. It can trace out the carbon backbone of an organic compound one carbon at a time. The low sensitivity of INADEQUATE has, however, limited its practical utility. 

A disadvantage is the naturally low sensitivity of the INADEQUATE technique. However, if one has enough substance (more than 5 mg per C atom, samples from syntheses), then the sophlstica-... 

Pulsed FT-NMR has facilitated the study of nuclei other than H where the sensitivity obtainable from a CW instrument is totally inadequate. In particular, 13C NMR, the sensitivity of which is nearly 10-4 less than that of the proton (Table 9.9), is now a well-established technique that yields information on the skeletal structure of complex molecules. The pulsed technique also enables proton spectra to be obtained from samples as small as a few micrograms. 

The US EPA has been concerned with neurotoxicity and sensitivity of children to pyrethroids (Sect. 5.1.2), and demanded pyrethroid registrants in the US to conduct developmental neurotoxicity (DNT) studies. However, the EPA concluded that a DNT study was inadequate for the evaluation of age-dependent sensitivity for pyrethroids, and asked interested parties to submit study protocols voluntarily to understand better the age-dependent sensitivity for pyrethroids (February 2010). To deal with this issue, the pyrethroid registrants in US formed a task force group, and proposed a new study design including PBPK modeling to the US EPA. 

An optical immunosensor for continuous T4 measurement has been described, in which the fluorescent indicator protein is separated from the sample flow chamber by a dialysis membrane.024) The indicator is T4-binding globulin (TBG), the intrinsic fluorescence (ex. 290 nm) of which is quenched by T4binding. Due to the high affinity of the TBG for thyroxine, the immunosensor is not reversible, but multiple measurements can be made until the TBG is saturated. Sensitivity is inadequate for clinically useful concentrations of T4, but suggestions for improvement of the method are made. 

An ultraviolet (UV) monitor is most commonly used in CE experiment. Such interaction studies using the ACE method can also be hampered by the inadequate sensitivity of UV detection. Fluorescence labeling and laser-induced fluorescence (LIF) detection have been employed to enhance the sensitivity of this method, as shown by the mobility-shift assay of fluorescence-labeled sugar caused by the interaction with the lectin, concanavalin A (74). When fluorescent dyes are employed for labeling, LIF detection provides several hundred times more sensitivity than UV detection. 

Tettanitroglycoluril is an expl more bri-sant than TNT, but comparable to PETN. it is extremely sensitive to impact and of inadequate thermal stability... 

End group analysis are restricted to relatively low molecular weight polymers. Chemical procedures for counting end groups are usually considered inadequate for polymers of molecular weights in excess of 20,000 to 30,000 [1], The sensitivity of the method decreases as the molecular weight of the polymer increases (see Note 1). 

Eckhardt (22) has remarked that the evolution of biological tests to screen for the hypersusceptible worker represents one of the important preventive health vistas in occupational health. The development of sensitive and specific biological markers of early medical sequelae of harmful exposures holds promise to allow the identification of inadequate exposure containment and unsafe exposure limits before irreversible impairment of health has occurred. 

Even in the setting of a classic infectious disease for which isolation techniques have been established for decades (eg, pneumococcal pneumonia, pulmonary tuberculosis, streptococcal pharyngitis), the sensitivity of the culture technique may be inadequate to identify all cases of the disease. 

A relatively new and promising area of research concerns the role of inadequate dietary calcium in the development of essential hypertension or high blood pressure (Villar et al. 1986 Karanja and McCarron 1986 Resnick 1985 NDC 1984A.B McCarron 1985, 1983, 1982 McCarron et al. 1982). While most reports relating diet to hypertension have emphasized sodium, it appears that only a small proportion of the U.S. population is genetically sodium sensitive and that for the majority, dietary sodium intake has little effect on blood pressure. As discussed below, inadequate calcium intake, either alone or in combination with other factors, appears to predispose to high blood pressure by a mechanism(s) as yet unknown. 

The antiphase relationship of the C13 —C13 doublet signals in the INADEQUATE spectrum can be eliminated by an additional spin-echo sequence (— 1/4Jcc — 180° — 1 /4 Jcc —) before the 90 monitor pulse [58]. The sensitivity of the experiment may be improved by the application of stronger magnetic fields or by using proton polarization transfer techniques [59]. 

The derivatization of fatty acids, and of acidic substances in general, has been a problem in analytical-organic chemistry for many years. The classically used derivatives have been amides and esters. The main problem in using methyl esters of fatty acid in HPLC is that one cannot then use the UV detector, because of inadequate absorption. Thus a search for an alternate method of forming UV-sensitive derivatives has been initiated in several laboratories. 

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