Chemical characterization substances

Betazole (683) has been used as a chemical control substance for pharmacological characterization of histamine receptors (B-80MI40406), and shows a relative selective activity towards the H2-receptor. Betazole hydrochloride is used to diagnose impairment of the acid-producing cells of the stomach. 

A secondary chemical reference substance is a substance whose characteristics are assigned and/or calibrated by comparison with a primary chemical reference substance. The extent of characterization and testing of a secondary chemical reference substance may be less extensive than for a primary chemical reference substance. This definition may apply to some substances termed Working Standards . 

The EPA GLPs include a paragraph under Subpart G ( 160.135) that deals with physical and chemical characterization studies. This paragraph states that all provisions of GLP standards apply to certain specific physical and chemical characterization studies of test, control, and reference substances. These studies are listed. It also states that certain specified paragraphs do not apply to studies other than those listed. 

Is the BCS that was developed with reference to chemically characterized and well-defined synthetic drug substances relevant for application and or adoption to botanical preparations (8) If one assumes, as is reasonable, that bioavailability of the active component(s) in a botanical dosage form depends on both solubility and permeability, the solubility of the botanical extract could be controlled through appropriate formulation technology and dissolution testing. The applicability of the BCS to botanical preparations will certainly be increasingly researched, debated, and discussed in the coming years. 

There are four different drug products under Part II chemical active substance(s), radiopharmaceutical products, biological medicinal products, and vegetable medicinal products. For example, the GMP production report for biological medicinal products includes description of the genes used, strain of cell line, cell bank system, fermentation and harvesting, purification, characterization, analytical method development, process validation, impurities, and batch analysis (GMP production of biopharmaceuticals is described in Chapter 10). A DMF (Exhibit 8.8) is submitted. 

We should keep in mind that the term "pesticide" refers to a chemical use category and not a specific chemical characteristic. It does impart the knowledge that a substance has toxic properties which can be used to advantage. Only with proper chemical characterization of residues found in the body and knowledge of their potential influence on homeostasis will it be possible to dispel popular misconceptions to the effect that pesticide chemicals are handled differently from other chemicals which enter the body or are unique in the hazards they present to the system. 

The chemical aspects of these studies focus primarily on the chemical characterization of the test substance and/or mixture. The identity of the test chemical should be proven, and the analytical procedures used, such as gas or liquid chromatography, nuclear magnetic resonance spectrometry, or nass spectroscopy, should be available for audit. This would include the chromatograms or spectra from these analyses. It is imperative that raw data be left intact as they emerge from an instrument to maintain data integrity. Chro-natographic printouts are to remain attached and in sequence. If some data points are not used in the final report, the reason is to be documented and those not used are to remain with the stud/ file. 

Relatively few biochemicals can be measured directly in natural waters because concentrations of individual compounds are low (nanomolar) and salts and other components often interfere with these analyses. DOM can be concentrated and isolated from natural waters for more thorough chemical characterization, and two approaches for DOM isolation, adsorption onto solid phases and ultrafiltration are now widely used. The adsorption of DOM onto XAD resins is used to isolate a fraction of DOM that is operationally defined as humic substances (Thurman, 1985). More recently, tangential-flow ultrafiltration with 1000 Da cutoff membranes has been used to isolate the high-molecular-weight or colloidal fraction of DOM (Benner et al., 1992, 1997). 

Humic substances account for 40-70% of the DOC in rivers and 5-25% of the DOC in the ocean (Table I). It is important to note that recoveries of adsorbed humic substances from XAD resins are not quantitative, so the chemical characteristics of the recovered humic substances are not necessarily representative of all the humic substances retained by the resin. Tangential-flow ultrafiltration retains 45-80% of the DOC in rivers and 25-40% of the DOC in the surface ocean (Table I). Essentially all of the DOC retained during ultrafiltration is recovered for chemical characterization. In general, ultrafiltration recovers a larger fraction of the DOM from these systems. These methods also isolate DOM based on different mechanisms. Adsorption onto XAD resins at low pH chemically fractionates the DOM and isolates the more hydrophobic components, whereas ultrafiltration principally separates components of DOM on the basis of size and shape. 

Figure 4.3. Gel permeation chromatograms of humic acids isolated from a soil either unamended (A) or amended with 25tha 1yr 1 of cattle manure for 4 years (B) and 25, 50, and 100tha 1yr 1 of sewage sludge for 4 years (C, D, and E, respectively). Reprinted from Piccolo, A., Zaccheo, E, and Genevini, P. G. (1992). Chemical characterization of humic substances extracted from organic-waste-amended soils. Bioresource Technol. 40, 275-282, with permission from Elsevier.

Piccolo, A., Zaccheo, P., and Genevini, P. G. (1992). Chemical characterization of humic substances extracted from organic-waste-amended soils. Bioresource Technol. 40, 275-282. 

Hoffer, A., Kiss, G., Blazso, M., and Gelencser, A. (2004). Chemical characterization of humic-like substances (HULIS) formed from a lignin-type precursor in model cloud water. Geophys. Res. Lett., 31, doi 10.1029/2003GL018962. 

In this scheme, the primary reference material is defined as a chemical substance of the highest (and known) purity, or a well-characterized substance in a matrix, This classification of materials is, however, fairly arbitrary. It is ideal when used in connection with standards characterized in terms of biological activity. Primary standards are thus the International Reference Preparations (IRP) produced by the World Health Organization (WHO). In this case the primary standard for a particular antibiotic is the WHO reference preparation which constitutes the unit of that antibiotic. When people wish to use it they have to prepare a large batch of samples calibrated to the primary. This is then called a secondary standard. However, for well-defined chemical parameters, the term certified reference material is preferred. 

Allochthonous DON sources from terrestrial runoff, plant detritus leaching, soil leaching, sediments, and atmospheric deposition may also represent important inputs to estuaries (Berman and Bronk, 2003). DON typically represents about 60 to 69% of the TDN in rivers and estuaries (Berman and Bronk, 2003). The major components of DON include urea, dissolved combined amino acids (DCAA), DFAA, proteins, nucleic acids, amino sugars, and humic substances (Berman and Bronk, 2003). However, less than 20% of DON is chemically characterized. 

Streng, W. H. (1997). Physical chemical characterization of drug substances. Drug Disc. Today, 2,415-26. [95, 240]... 

Holcomb D. W. (1979) Chemical characterization of swamp peat humic substances. MS Thesis, Georgia Institute of Technology, 63pp. 

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