Specific activity

Chemical purity measurements are often not performed on tritiated compounds of high specific activity. Such materials are usually prepared in submilligram quantities, and, even if it were feasible to weigh samples accmately enough to prepare solutions of known mass concentration, the required manipulations would increase the risk of decomposition of the compound (see Section 1.5). Fortunately, high specific activity tritiated compounds are 

Measurements of enantiomeric purity are most conveniently accomplished using chiral HPLC analysis against authentic samples of enantiomerically pure and racemic materials. Alternative methods include NMR with a chiral shift reagent and optical rotation measurements. 

Since it is relatively common that compounds coelute or nearly coelute in even high-resolution chromatographic systems, it is always recommended that radiochemical purity analyses be carried out in two different chromatographic systems, as unlike one another as possible. For example, the combination of one reverse-phase HPLC or TLC method and one normal-phase HPLC or TLC method is usually recommended, but two reverse-phase HPLC analyses using different column types and mobile phases may also be acceptable. 

It should be noted that these chromatographic-radiometric methods have inherent shortcomings that must be understood and taken into account both in the chromatography component and the radiodetection component of the assay. 

The chromatographic part in HPLC, there is the possibihty that one or more radioactive components are not detected because they fail to exit the column by the end of the monitoring period. An effective check for this possibility is to measure the quantity of 

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The capital cost estimates are generated by the Engineering function, often based on 50/50 estimates (equal probability of cost overrun and underrun). It is recommended that the operating expenditure is estimated based on the specific activities estimated during the field lifetime (e.g. number of workovers, number of replacement items, cost of forecast manpower requirements). In the absence of this detail it is common, though often inaccurate, to assume that the opex will be composed of two elements fixed opex and variable opex. 

Tajima and co-workers [108] determined the surface excess of sodium dode-cyl sulfate by means of the radioactivity method, using tritiated surfactant of specific activity 9.16 Ci/mol. The area of solution exposed to the detector was 37.50 cm. In a particular experiment, it was found that with 1.0 x 10" Af surfactant the surface count rate was 17.0 x 10 counts per minute. Separate calibration showed that of this count was 14.5 X 10 came from underlying solution, the rest being surface excess. It was also determined that the counting efficiency for surface material was 1.1%. Calculate F for this solution. 

As a conclusion one can say that the distinction of islands of specific activity from within a sea of baseline toxicity, with each island representing a local chemical biological mechanism domain, is still a challenge to be solved by scientists working both experimentally and computationally. 

Single compact sources of Cobalt-60 vary from about 1 to 10/curie, depending on quantity and specific activity. 

It is reported that mild carbon steels may be effectively protected by as little as 55 ppm of KTc04 in aerated distilled water at temperatures up to 250oC. This corrosion protection is limited to closed systems, since technetium is radioative and must be confined. 9sTc has a specific activity of 6.2 X lOs Bq/g. Activity of this level must not be allowed to spread. 99Tc is a contamination hazard and should be handled in a glove box. 

Searches for the element on earth have been fruitless, and it now appears that promethium is completely missing from the earth s crust. Promethium, however, has been identified in the spectrum of the star HR465 in Andromeda. This element is being formed recently near the star s surface, for no known isotope of promethium has a half-life longer than 17.7 years. Seventeen isotopes of promethium, with atomic masses from 134 to 155 are now known. Promethium-147, with a half-life of 2.6 years, is the most generally useful. Promethium-145 is the longest lived, and has a specific activity of 940 Ci/g. 

Most chemical iavestigations with plutonium to date have been performed with Pu, but the isotopes Pu and Pu (produced by iatensive neutron irradiation of plutonium) are more suitable for such work because of their longer half-Hves and consequendy lower specific activities. Much work on the chemical properties of americium has been carried out with Am, which is also difficult to handle because of its relatively high specific alpha radioactivity, about 7 x 10 alpha particles/(mg-min). The isotope Am has a specific alpha activity about twenty times less than Am and is thus a more attractive isotope for chemical iavestigations. Much of the earher work with curium used the isotopes and Cm, but the heavier isotopes... 

The ideal plant growth regulator should leave no harmful persistent residue in a finished product or crop and the paradigm compounds are ones that have high specific activity, are target specific, and are environmentally biodegradable. 

The conditions whereby dandmff, seborrheic dermatitis, and psoriasis dmg products are generally recognized as safe and effective and are not misbranded is available (70). Specific active iagredients that can be used as well as the statement of identity, iadications for use, and required warnings, are identified. Products that do not meet all of these requirements are considered new dmgs and must have an approved NDA for the nonmonograph conditions. 

Reverberation Control. Reverberation time (T q) is defined as the length of time in seconds for the sound of an instantaneously stopped source in a room to decay by 60 decibels (dB). Reverberation time is one important factor in determining the acoustical character of a space and its suitabiHty for specific activities. For lectures and other speech activities a relatively short reverberation time is desirable so that syllables do not persist and overlap one another, causing difficulty with inteUigibiHty conversely, for music activities, a relatively long reverberation time is desirable to allow blending of the sound and a sense of being surrounded by the music. Without reverberation music usually sounds dull and lifeless. 

Activated diffusion of the adsorbate is of interest in many cases. As the size of the diffusing molecule approaches that of the zeohte channels, the interaction energy becomes increasingly important. If the aperture is small relative to the molecular size, then the repulsive interaction is dominant and the diffusing species needs a specific activation energy to pass through the aperture. Similar shape-selective effects are shown in both catalysis and ion exchange, two important appHcations of these materials (21). 

Direct quantitation of receptor concentrations and dmg—receptor interactions is possible by a variety of techniques, including fluorescence, nmr, and radioligand binding. The last is particularly versatile and has been appHed both to sophisticated receptor quantitation and to dmg screening and discovery protocols (50,51). The use of high specific activity, frequendy pH]- or p lj-labeled, dmgs bound to cmde or purified cellular materials, to whole cells, or to tissue shces, permits the determination not only of dmg—receptor saturation curves, but also of the receptor number, dmg affinity, and association and dissociation kinetics either direcdy or by competition. Complete theoretical and experimental details are available (50,51). 

Isotope CAS Registry Number Half-hfe, Specific activity, Bq/mmol Eneigy, MeV, % Decay product... 

Syntheses of radioactive tracers involve all of the classical biochemical and synthetic chemical reactions used in the synthesis of nonradio active chemicals. There are, however, specialized techniques and considerations required for the safe handling of radioactive chemicals, strategic synthetic considerations in terms of their relatively high cost, and synthesis scale constraints governed by specific activity requirements. 

Many applications ia tracer technology require products of high specific activity, ie, compounds having a high degree of substitution of specific atoms with radioisotopes. For many labeled compounds nearly 100% labeling can be achieved at one or more locations ia a molecule usiag... 

The introduction of tritium into molecules is most commonly achieved by reductive methods, including catalytic reduction by tritium gas, PH2], of olefins, catalytic reductive replacement of halogen (Cl, Br, or I) by H2, and metal pH] hydride reduction of carbonyl compounds, eg, ketones (qv) and some esters, to tritium-labeled alcohols (5). The use of tritium-labeled building blocks, eg, pH] methyl iodide and pH]-acetic anhydride, is an alternative route to the preparation of high specific activity, tritium-labeled compounds. The use of these techniques for the synthesis of radiolabeled receptor ligands, ie, dmgs and dmg analogues, has been described ia detail ia the Hterature (6,7). 

The small synthetic scale used for production of many labeled compounds creates special challenges for product purification. Eirst, because of the need for use of micro or semimicro synthetic procedures, the yield of many labeled products such as high specific activity tritiated compounds is often low. In addition, under such conditions, side reactions can generate the buildup of impurities, many of which have chemical and physical properties similar to the product of interest. Also, losses are often encountered in simply handling the small amounts of materials in a synthetic mixture. As a consequence of these considerations, along with the variety of tracer chemicals of interest, numerous separation techniques are used in purifying labeled compounds. 

Eor products having relatively low specific activity, such as some compounds labeled with and which are synthesized on the scale of several millimoles, classical organic chemical separation methods may be utilized, including extraction, precipitation, and crystallization. Eor separation of complex mixtures and for products having high specific activity, such as those labeled with tritium, etc, chromatographic methods utilizing paper, thin... 

A related mechanism of degradation involves the direct interaction of the radioactive emission with other tracer molecules in the preparation. This phenomenon is likely to occur in high specific activity compounds stored at high radiochemical concentrations in the absence of free-radical scavengers. 

Other methods of sensitive detection of radiotracers have been developed more recently. Eourier transform nmr can be used to detect (nuclear spin 1/2), which has an efficiency of detection - 20% greater than that of H. This technique is useful for ascertaining the position and distribution of tritium in the labeled compound (14). Eield-desorption mass spectrometry (fdms) and other mass spectral techniques can be appHed to detection of nanogram quantities of radiolabeled tracers, and are weU suited for determining the specific activity of these compounds (15). 

An important consideration for all radiopharmaceuticals and especially radiolabeled biologically active molecules is specific activity. There are two types of specific activity radionucHdic and biological. RadionucHdic specific activity refers to the ratio of the number of atoms of a particular radioisotope to the total number of atoms of the element. For Tc, the radionuchdic specific activity is the number of Tc atoms to the total number of Tc and Tc atoms. Because all isotopes of an element ate chemically identical, a low specific activity may lead to a low yield in the synthesis of a radiopharmaceutical if a significant proportion of the reagents is consumed by the undesited isotopes. 

AH cephalosporins found in nature (Tables 1 and 2) have the D-a-aminoadipic acid 7-acyl side chain (21). AH of these compounds can be classified as having rather low specific activity. A substantial amount of the early work in the cephalosporin area was unsuccessfiiHy directed toward replacing the aminoadipic acid side chain or modifying it appropriately by fermentation or enzymatic processes (6,22). A milestone ia the development of cephalosporins occurred in 1960 with the discovery of a practical chemical process to remove the side chain to afford 7-ACA (1) (1). Several related processes were subsequendy developed (22,23). The ready avaHabHity of 7-ACA opened the way to thousands of new semisynthetic cephalosporins. The cephalosporin stmcture offers more opportunities for chemical modification than does that of penicillins There are two side chains that especiaHy lend themselves to chemical manipulation the 7-acylamino and 3-acetoxymethyl substituents. 

Specifications. Activated carbon producers furnish product bulletins that Hst specifications, usually expressed as a maximum or minimum value, and typical properties for each grade produced. Standards helpful in setting purchasing specifications for granular and powdered activated carbon products have been pubHshed (33,34). 

For purposes of dosage, the specific activity of an enzyme is usually expressed as International Units (lU) rather than in terms of weight. However, unit measurements do not provide information on the absolute purity of a given product. Moreover, purity is not as critical an attribute for oral enzymes, as opposed to those adrninistered parenteraHy, inasmuch as the gastrointestinal tract is capable of disposing of most inert contaminants. 

Enzymes are excellent catalysts for two reasons great specificity and high turnover rates. With but few exceptions, all reac tions in biological systems are catalyzed by enzymes, and each enzyme usually catalyzes only one reaction. For most of the important enzymes and other proteins, the amino-acid sequences and three-dimensional structures have been determined. When the molecular struc ture of an enzyme is known, a precise molecular weight could be used to state concentration in molar units. However, the amount is usually expressed in terms of catalytic activity because some of the enzyme may be denatured or otherwise inactive. An international unit (lU) of an enzyme is defined as the amount capable of producing one micromole of its reaction product in one minute under its optimal (or some defined) reaction conditions. Specific activity, the activity per unit mass, is an index of enzyme purity. 

If both frequency and consequence values are calculated and reported on an absolute basis, then they may be reported graphically in combination with one another (Chapter 3), or simply as the product of frequency and consequence. Table 5 contains some examples of typical risk estimates (frequency and consequence products). Based on absolute risk estimates, you can decide whether the risk of a specific activity exceeds your threshold of risk tolerance (risk goal). If so, analysts can estimate the reduction in risk, given that certain improvements are made, assumptions changed, or operating circumstances eliminated. 

Urokinase (from human urine) [9039-53-6] Mr 53,000, [EC 3.4.21.31]. Crystn of this enzyme is induced at pH 5.0 to 5.3 (4") by careful addition of NaCl with gentle stirring until the soln becomes turbid (silky sheen). The NaCl concentration is increased gradually (over several days) until 98% of saturation is achieved whereby the urokinase crystallises as colourless thin brittle plates. It can be similarly recrystd to maximum specific activity [104K CTA units/mg of protein (Sherry et al. J Lab Clin Med 64 145 1964)]. [Lesuk et al. Science 147 880 1965 NMR Bogusky et al. Biochemistry 28 6728 1989.] It is a plasminogen activator [Gold et al. Biochem J 262 1989 ]. 

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