Reference Substance Available

The simplest qualitative analysis involves a comparison of the retention times between a chromatographic peak containing an unknown compound and peaks obtained for reference samples using more than one stationary phase. 

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The pseudo-critical values were tested, with 0, 6 and set equal to unity, by comparison of predicted compressibility factors with the experimentally determined values for hydrogen and methane mixtures. The value of a was taken from a correlation developed earlier for high temperature systems [7] shown in Table V. The only pure reference substances available with known compressibility factors were methane, hydrogen and deuterium. The critical constants used for these gases are given in Table IV. 

The amounts of the standard isotopic species and the tracer isotopic species are represented by X and X for the sample and the reference material. The reference substance is chosen arbitrarily, but is a substance that is homogeneous, available in reasonably large amounts, and measurable using standard analytical techniques for measuring isotopes (generally mass spectrometry). For instance, a sample of ocean water known as Standard Mean Ocean Water (SMOW) is used as a reference for and 0. Calcium carbonate from the Peedee sedimentary formation in North Carolina, USA (PDB) is used for C. More information about using carbon isotopes is presented in Chapter 11. 

The Pharmacopoeial Forum fulfills a vital role in promoting industry-wide communication between those involved with quality assurance, the development of standards and analytical methods. It contains an up to date list of official USP Reference Substances, with current and recently changed lot numbers. Reference Substances not yet available and those under development are also described. The publication acts as an international open forum in which scientists are invited to express their views, suggestions, ideas and comments regarding new drug standard development and revisions to existing monographs. Pharmacopoeial Forum is published, on a subscription basis, six times a year, back issues are available for USP website see Table 84. 

The Promochem Group was the first international specialist supplier of certified reference materials (CRMs) and pharmaceutical reference substances used in environmental, medical and trace element analysis. Their experience provides a viewpoint that echoes, reinforces and expands on many of the trends discussed above (Jenks 1997). From the middle of the 1980 s, sales of CRM by Promochem increased between 10 % and 20 % annually, depending on the market sector and application. Since then National and International Metrology Institutes, such as the now privatized U.K. Laboratory of the Government Chemist (LGC), the European and U.S. Pharmacopoeias, the E.U. IRMM and others have recognized that efficient distribution of RMs, backed by available technical support, is as important as production and certification. Thus, they have moved to spread their influence outside their national origins. The Web and e-commerce will continue to grow as major facilitators of better information dissemination and supply of CRMs. 

Several useful methods are available for extrapolating equilibrium data for a given system to various temperatures and pressures. One convenient method is by use of a reference substance plot. Here, the adsorption equilibrium partial pressure of the adsorbate is plotted against a pure substance vapor pressure, preferably that of the adsorbate. If logarithmic coordinates are used on both axes, lines of constant adsorbent loading, isosteres, are linear for most substances. Therefore, only two datum points are required to establish each isostere. 

An alternative technique involves adjusting diffusivities known for one chemical to approximate values for chemicals of related structure, recognizing that molecular velocities and thus molecular diffusivities vary roughly inversely with the square root of molecular mass (Eq. 18-38). We can use this readily available parameter to adjust the known diffusivity of a reference substance to the unknown diffusivity of substance i according to the following equation ... 

Other reference substances are available and can be used as well. Sometimes the resonance of the actual solvent can serve as a reference. Preferably, the referencing method used for the sample should be the same as that used for the authentic reference sample (or library spectrum), or at least the scale... 

Reference ANZECC/ARMCANZ (2000) CCME (1999a) Lepper (2005) and environmental quality standards (EQSs) Substance data sheets for the EU priority substances (available at http //forum.europa.eu.int/ Public/irc/env/wfd/library l= /framework directive/i-priority substances/supporting background/ substance sheets vm= detailed sb= Title) Procedures for the Derivation of Equilibrium Partitioning Sediment Benchmarks (ESBs) for the Protection of Benthic Organisms. Consult http // www.epa.gov/nheerl/ publications/ for these procedures for PAH mixtures, dieldrin, endrin, and heavy metals. 

The use of distributed pharmacokinetic models to estimate expected concentration profiles associated with different modes of drug delivery requires that various input parameters be available. The most commonly required parameters, as seen in Equation 9.1, are diffusion coefficients, reaction rate constants, and capillary permeabilities. As will be encountered later, hydraulic conductivities are also needed when pressure-driven rather than diffusion-driven flows are involved. Diffusion coefficients (i.e., the De parameter described previously) can be measured experimentally or can be estimated by extrapolation from known values for reference substances. Diffusion constants in tissue are known to be proportional to their aqueous value, which in turn is approximately proportional to a power of the molecular weight. Hence,... 

The extent of the system suitability testing is dependent on, for example, the stage of drug development, the objective of the analytical procedure, the availability of reference substances, etc. The following parameters may be considered " " ... 

HPLC-UV diode-array detection (DAD) or HPLC-MS techniques take advantage of chromatography as a separation method and DAD or MS as identification and/or quantification methods. Both DAD and MS can rapidly provide on-line UV and MS information for each individual peak in a chromatogram. In most cases, the identification of the peaks can be made directly on-line by comparison with literature data or with standard compounds. However, when no standard compounds are available, the rapid preliminary identification process becomes significantly more complex. The general identification problem in bioprocess monitoring described below exists in all cases when a new biotechnological process is initiated and when the product is not available as a reference substance. 

The BP Commission can also call on expertise available in the British Pharmacopoeia laboratories situated in the premises of the Laboratory of the Government Chemist in West London. The BP laboratory carries out and validates assay procedures for the Commission and in addition, is responsible for the procurement, establishment, maintenance and sale of British Pharmacopoeia Chemical Reference Substances (BPCRS). These reference substances, as their name suggests, are authentic samples of a drug or decomposition product which are used as standards in a drug assay. The BP laboratory also fulfils an important forensic role in the control of counterfeit medicines. With the advent of the internet, the public can easily gain access to supplies of prescription-only medicines online. These medicines are often adulterated, contaminated or simply counterfeit, and comparison with authentic samples is necessary to ensure that the correct preparation is supplied. 

The Committee recommended that the report be adopted. It also recommended that all efforts be made to maintain this important programme and endorsed the efforts made by the Secretariat to ensure financial support for the activities of the WHO Collaborating Centre for Chemical Reference Substances. It recognized that there was a need to further promote the availability and use of ICRS. 

List of available International Chemical Reference Substances (ICRS) (Annex 1). 

Once this function is determined, it could be applied to any substance, provided its critical constants Pc, T, and V are known. One way of applying this principle is to choose a reference substance for which accurate PVT data are available. The properties of other substances are then related to it, based on the assumption of comparable reduced properties. This straightforward application of the principle is valid for components having similar chemical structure. In order to broaden its applicability to disparate substances, additional characterizing parameters have been introduced, such as shape factors, the acentric factor, and the critical compressibility factor. Another difficulty that must be overcome before the principle of corresponding states can successfully be applied to real fluids is the handling of mixtures. The problem concerns the definitions of Pq P(> and Vc for a mixture. It is evident that mixing rules of some sort need to be formulated. One method that is commonly used follows the Kay s rules (Kay, 1936), which define mixture pseudocritical constants in terms of constituent component critical constants ... 

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