Standards RM

Each future RM for hydrogen exchange measurements must be a Type A protein (see Section 4.2), so that connection to the SI is maintained. The protein ensemble should comprise a single 

The quality and utility of each RM will be greatly enhanced by the availability of a set of amide exchange rate coefficients derived from measurements by an orthogonal method, such as HX-NMR. The physical properties of proteins and their behaviors during proteolysis vary considerably. The optimum set of reference proteins should reflect these varied behaviors. This will enable researchers to pair the measurement difficulties of their commercial biotherapeutic product with a primary RM. The chosen primary RM can then be used to measure HX-MS laboratory performance over time and location. 

Thus far, no national standards laboratory (e.g., NIST) or private standards organization has issued, or recommended, suitable proteins for use in an HX-MS calibration hierarchy. This absence is not surprising, as investigators using HX-MS have yet to settle on a set of consensus standard RM. In view of the rapid expansion in the use of HX-MS for research applications and its likely future applications as a quality control for biopharmaceuticals, perhaps it is time for the HX-MS community, the national standards laboratories, and RM producers to devote resources to identifying and characterizing proteins that can serve as suitable reference proteins. 

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Let us begin with the ISO definition [9] A calibration is a set of operations that establish, under specified conditions, the relationship between values of quantities indicated by a measuring instrument or measuring system, or values represented by a material measure or reference material, and the corresponding values realized by standards. Applied to amount measurements, the standards would then be the values assigned to the RMs (of defined composition) at the stated uncertainty relative to the true value of the property, expressed in SI units, or relative to an internationally recognized, certified standard RM for the relevant property, range, and matrix composition. 

FIGURE 15.1 An overview of the natural variations in the carbon isotopic composition of a range of materials. Reprinted from T.B. Coplen et al. [16], with permission from Coplen. NBS, National Bureau of Standards L-SVEC, lithium carbonate IAEA, International Atomic Energy Agency NGS, natural gas standards RM, reference material CAM, Crassulacean acid metabolism USGS, U.S. Geological Survey VPDB, Vienna PeeDee Belemnite. 

There may he as many basis sets defined for polyatomic calculations as there are cpiantum chemists One would like to define, m advance, the standard basis sets that will he suitable to most users. However, one also wants to allow sophisticated users the capability to modify existing basis sets or define their own basis sets. We have thus defined a IlyperChem basis set file format and included with IlyperChem a number of these. BAS files that define standard basis sets. Users, however, can define as many of their own basis sets as they like using Ih is file formal. The details of th e IlyperChem basis set file formal are described in the IJypcrChcm iie.fe.rm ce m anital. 

The RMS-800 provides steady-shear rotational rates from 10 to 100 rad/s and oscillatory frequencies from 10 to 100 rad/s. An autotension device compensates for expansion or contraction. With the standard 25- and 50-mm parallel plates, the viscosity range is 50-10 mPa-s, and the shear modulus range is 8 x 10 to 10 N/m. These ranges can be expanded with nonstandard plates, cones, and a Couette system. The temperature range is 20-350°C (-150 0 optional). 

Acylation. To achieve acylation of thiophenes, acid anhydrides with phosphoric acid, iodine, or other catalysts have been widely used. Acid chlorides with AlCl, SnCl, ZnCl2, and BF also give 2-thienylketones. AH reactions give between 0.5 and 2.0% of the 3-isomer. There has been much striving to find catalyst systems that minimize the 3-isomer content attempting to meet to customer specifications. The standard procedure for formylation is via the Vil smeier-H a ack reaction, using phosphoms o xycbl o ri de / /V, / V- dim e tb yl fo rm a m i de (POCl /DMF) or /V-m ethyl form an i1 i de. 

To gather information which will enable selection of appropriate control equipment. If a source test determines that the emission is 3000 mg of particulate per cubic meter and that it has a weight mean size of 5 p.m, a control device must be chosen which will collect enough particulate to meet some required standard, such as 200 mg per cubic meter. (4) To determine the efficiency of control equipment installed to reduce emissions. If a manufacturer supplies a device guaranteed to be 95% efficient for removal of particulate with a weight mean size of 5 /rm, the effluent stream must be sampled at the inlet and outlet of the device to determine if the guarantee has been met. 

A novel cross-linked polystyrene-divinylbenzene copolymer has been produced from suspension polymerization with toluene as a diluent, having an average particle size of 2 to 50 /rm, with an exclusive molecular weight for the polystyrene standard from about 500 to 20,000 in gel-permeation chromatography. A process for preparing the PS-DVB copolymer by suspension polymerization in the presence of at least one free-radical polymerization initiator, such as 2,2 -azo-bis (2,4-dimethylvaleronitrile) with a half-life of about 2 to 60 min at 70°C, has been disclosed (78). 

The model is sensitive to lower river sediment oxygen demand. If the demand is removed, the predicted DO value at RK 3.1 (RM 5.0) is 8 percent higher than the standard condition. 

Experience has shown that correlations of good precision are those for which SD/RMS. 1, where SD is the root mean square of the deviations and RMS is the root mean square of the data Pfs. SD is a measure equal to, or approaching in the limit, the standard deviation in parameter predetermined statistics, where a large number of data points determine a small number of parameters. In a few series, RMS is so small that even though SD appears acceptable, / values do exceed. 1. Such sets are of little significance pro or con. Evidence has been presented (2p) that this simple / measure of statistical precision is more trustworthy in measuring the precision of structure-reactivity correlations than is the more conventional correlation coefficient. 

In the United Kingdom chemical RMs were first produced some time in the late 1960 s at the National Physical Laboratory (NPL) Division of Chemical Standards at Teddington. This Division was transferred to the Laboratory of the Government Chemist LGC in November 1978. Early work was based on the development of highly... 

From the mid 1980 s the rise of Quahty Standards, Total Quahty Management and Accreditation schemes created a booming demand for RMs and CRMs. Thus, the use and production of matrix RMs rapidly increased the new IAEA database lists 56 producers from 22 cormtries and about 1640 RMs. The 1998 Comar database, which covers a much wider scope, hsts more than 200 producers and around 10 000 RMs see Chapter 8 for more details. 

The key difference between a CRM and an RM is the traceability. In order to play any role at aU in metrology, traceability is a key property. Traceability refers to a property value of the CRM, and thus to the underlying measurements. Insufficient traceability of these measurement results will eventually lead to a RM that cannot be certified, as the property value cannot be related to other standards. In the ideal case, traceability is realized up to the International System of Units, SI, but this is only feasible for a very small number of CRMs. 

There are two main uses of a RM calibration and method performance checking. ISO Guide 32 (1997) deals with the use of RMs for calibration purposes. RMs used for calibration purposes are usually RMs prepared by synthetic means. Commonly, the property values of these RMs are known from preparation, and verified by some kind of suitable measurement technique. This can be a technique directly providing a value for a property of interest, or a technique that allows the comparison of the new material against older measurement standards. 

ISO Guide 32 provides guidance in two ways. Apart from the guidance on using RMs for calibration purposes, it also provides information on the preparation and use of calibrants in a laboratory, and checking them against other RMs or measurement standards. 

A limited number of pure substances are available from NIST, primarily clini-cally-relevant compounds such as cholesterol, urea, uric acid, creatinine, glucose, cortisol, tripalmitin, and bilirubin (NIST SRM website). These compounds are certified for purity (greater than 99 %) and are used as primary calibrants in definitive methods for these clinical analytes (see below). Several additional pure substances are available for specific applications such as microchemistry, i.e. elemental composition (acetanilide, anisic acid, cystine nicotinic acid, o-bromobenzoic acid, p-fluoro-benzoic acid, m-chlorobenzoic acid), polarimetric standards (sucrose and dextrose), acidimetric standard (benzoic acid and boric acid). Only three pure substance NIST RMs are available for environmental contaminants, namely the chlorinated pesticides, lindane, 4,4 -DDT, and 4,4 -DDE. 

Schantz MM, Demiralp R, Greenberg RR, Hays MJ, Parris, RM, Porter BJ, Poster DL, Sander LC, Schiller SB, Sharpless KS, and Wise SA (1997a) Certification of a frozen mussel tissue standard reference material (SRM 1974a) for trace organic constituents. Fresenius J Anal Chem 358 431-440. 

Apart from innovative work, RMs are essential during exerdses such as the introduction to a laboratory of a method from elsewhere or the transfer of an established method onto new instrumentation. Even where the conditions for the analysis have been standardized by the manufacturer of a reagent kit, some validation work should still be undertaken so as to have documented data for quality assurance purposes, e.g. accreditation, as a basis for IQC, for later reference when problems which may be related to equipment, reagents or staff etc. need to be investigated. 

For many analytical methods there are no CRMs. It may also be that there is no primary standard, e.g. for determinations of enzyme activity, or that reliable methods for accurate determination do not exist. However, there is a requirement for RMs of some type. Samples which have previously been used within an FQA scheme may fulfil this purpose. When a large enough number of independent observations are made the mean is a good approximation to the true value (Sutton et... 

Data derived from analysis of RMs in EQA schemes may be informative and, as discussed above, help to direct and stimulate the laboratory towards providing results in the day to day work, which are accurate, precise and appropriate to the needs for which they were requested. Alternatively a scheme may operate simply to identify poor performance, so as to prohibit laboratories from carrying out certain tasks. The disadvantage of just an educational objective is that there are no sanctions to ensure that poor performance does not continue without being corrected. With licensing, if a laboratory is seen to fail, they wiU lose income and, to avoid controversy, the analytical standards may be set at a very low level so that only the grossly incompetent are eliminated. 

Thus, to further the goals of quality and good analytical practice for which RMs are intended, EQA schemes should combine some aspects of both objectives according to the political purposes for which the scheme is being organized. Whether used for educational or licensing purposes, the ultimate intention is to ensure a certain standard of analysis is achieved and maintained in order that the user of results may be protected against errors which could be costly, in financial or human terms. 

ATCC biological standards were known as Type Strains (TS), but as they are used in the same ways as, and fill many of the requirements for, RMs we have described them in this article as biological RMs. 

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