Certified analytical standard

Until relatively recently a major problem in developing chemical analytical methods for PSP toxins was the unavailability of analytical standards. These compounds (Figure 11.7) are extremely hygroscopic and thus can not be weighed reliably even if the purity can be established somehow it is impractical to synthesize them in useful quantities and they are found in nature as mixtures of closely related structures (Figure 11.7) that are not easy to separate. This is nowadays a major problem for regulatory laboratories that require certified analytical standards and reference materials in order to conduct accurate... 

For standard or proprietary polymer additive blends there is the need for analytical certification of the components. Blend technology has been developed for two- to six-component polymer additive blend systems, with certified analytical results [81]. Finally, there exist physical collections of reference additive samples, both public [82] and proprietary. The Dutch Food Inspection Service reference collection comprises 100 of the most important additives used in food contact plastics [83-85]. Reference compounds of a broad range of additives used in commercial plastics and rubber formulations are generally also available from the major additive manufacturers. These additive samples can be used as reference or calibration standards for chromatographic or spectroscopic analysis. DSM Plastics Reference Collection of Additives comprises over 1400 samples. 

In the field of RM certification, NAA represents a major analytical technique. It possesses unique quality assurance and self-verification aspects. Not surprisingly, therefore, NAA has been used to certify NIST standard reference materials [470]. By analogy, NAA has also been instrumental in analysing the EC polymer reference materials within the framework of the PERM project [1]. NAA was also used to validate a TXRF procedure for the determination of additives containing Ti, Zn, Br, Cd, Sn, Sb and Pb [56],... 

No standard reference materials have been certified for analysis of chlorobomanes, although several may be suitable — including fish oils and whale blubber. Analytical standards for several chlorobomanes are now available, but there is a need to identify other remaining environmentally significant congeners (Muir and de Boer 1993). More research is now recommended in the following areas ... 

At least one of the standards (the one used for initial calibration or the ICV standard) must be certified traceable to a national standard, such as the NIST-traceable standard reference materials. Certified stock standard solutions for the majority of environmental pollutants are available commercially. However, whether a stock standard is a certified solution or has been prepared by the laboratory, dilution errors during the standard preparation and analyte degradation in storage happen. The laboratories are able to detect such errors only by preparing and analyzing an independent, second source confirmation standard. 

Regarding laboratory controls, a review of laboratory notebooks and chromatograms should be done to check the reliability and authenticity of the supporting data in the methods development and testing of the clinical, bio, and stability batches. Reference standards used should be certified as standards. The FDA expects that, for bulk substances, the suitability of reference standards should be more extensive than that of bulk drug substance specifications. A comparison of analytical methods and specifications for lots of drug substance used in clinical batches and biobatches should be performed to see if any deletions or revisions to any specifications occurred. 

PTXs have been found in shellfish from most regions of the world, reflecting the world-wide distribution of Dinophysis spp. There is relatively little information on concentrations of PTXs in shellfish due to the previous scarcity of analytical standards and because monitoring for PTXs by instrumental methods has until recently not been widespread, but the bulk of the published information is summarized in Table 9.3. A certified reference material (CRM) for PTX-2 became available from the Certified Reference Materials Program (CRMP) of the National Research Council of Canada (Institute for Marine Biosciences, Halifax http //imb-ibm.mc-cmc.gc.ca/cimp/shellfisli/index e.php) in 2003 (Quilliam 2004), and a CRM for PTX-11 is expected in 2006 (M.A. Quilliam, personal communication). The availability of such standards should result in an increasing amount of reliable information on the type and concentration of PTXs present in natmal samples. 

It is worth mentioning that certified reference data were not available for the elements aluminum, titanium, vanadium, boron, nickel, and phosphorus at the time of analysis. This is a frequent problem in multielement analyses. It is diflBcult to obtain standard biological reference materials similar to the samples being analyzed with more than but a few certified analytical results. The lack of standard reference material limits quality assurance review of the data and diagnosis of analytical problems. The recent issue of new standards such as spinach leaves and brewers yeast will improve the material variety. Certification of more elements in the existing standards will also greatly assist the analyst. 

It is considered good practice to know the concentration of the spike (although this is not strictly necessary as the IDMS measurement is actually based on a natural calibration standard of the analyte). If a certified spike standard is unavailable, the concentration of the spike is determined by a reverse IDMS measurement using the natural calibration standard. 

A reliable supply of analytical standards is crucial for quantitative analysis of POPs. Unless the laboratory has good facilities for storage and handling of pure, crystalline standards, it is preferable to purchase analytical standards in pre-certified solutions from commercial suppliers. These standards must be stored so as to limit evaporation of solvent. Working standards are prepared, in the solvent used for gas chromatography (GC) injection, from a more concentrated solution for daily or weekly use. 

It is very important and the most important task for the analyst who is responsible for operation and maintenanee of analytical instrumentation. Calibration is followed by a verifieation proeess in which specifications can be established and the analyst ean evaluate whether or not the calibration is verified or refuted. A calibration that has been verified can be used in acquiring data from samples for quantitative analysis. A calibration that has been refuted must be repeated until verification is achieved, e.g., if, after establishing a multipoint calibration for benzene via a gas chromatographie determinative method, an analyst then measures the concentration of benzene in a certified reference standard. The analyst expects no greater than a 5% relative error and discovers to his surprise a 200% relative error In this case, the analyst must reconstruct the calibration and measure the certified reference standard again. Close attention must be paid to those sourees of... 

In order to obtain reliable results for quantification purposes, the quality parameters of the methods developed need to be studied. Only two developed UHPLC-MS/ MS methods have been validated in the literature. One study was validated by using the National Institnte of Standards and Technology (NIST) Certified Reference Material (CRM) [18], and the second by spiking the extraction solution with different concentrations of procyanidin and alkaloid [29]. The LOQs obtained for catechin and epicatechin were 11.2 and 65.5 pg/g of chocolate when the NIST CRM was nsed [18], On the other hand, when the extraction solution was spiked with the target analytes standards, the detection limits (LODs), and LOQs of the procyanidins (catechin, epicatechin, and the dimer Bj) were between 7 and 30 pg/L and 10 and 90 pg/L, respectively, and for the caffeine and teobromine alkaloids, these values were below 30 and 100 pg/L, respectively [26]. 

The traceability of the result of a measurement is defined as the property of the result whereby it can be related to stated references, usually national (NIST, NRC, etc.) or international (CSA and EU) standards, through an unbroken chain of comparisons all with stated uncertainties, e.g.. Figure 2.1. As applied to an analytical standard, distinct from a measurement of an unknown concentration, this concept implies that the purity of the standard has been determined by a traceable sequence of analytical steps, each with a known uncertainty, that permit comparison with a certified reference material (CRM) (Section 2.2.2) from a recognized supplier. This procedure results in a Certificate of Analysis, discussed in Section 2.2.2 for CRMs and also in Section 9.4.4c with respect to the analytical (reference)... 

CRMs can be either analytical standards (Section 2.2.1), or calibration solutions that are solutions of an analytical standard at a certified concentration in a clean solvent, or natural material (matrix) CRMs that are prepared from material found in nature, i.e., are surrogates for the real samples to be analyzed. Matrix CRMs are invaluable as tools in quality assurance and quality control (QA/QC) in analytical laboratories, as discussed in Chapter 10. However, CRMs are generally too expensive to be used as everyday QCs and are generally used as method development tools or in occasional checks of the laboratory QCs (Section 2.5.3). 

To qualify as certified, aU reference materials must be prepared and characterized in accordance with a strict set of guidelines set out in ISO Guide 34-2000 a user s guide to this ISO document is available (ILAC 2000). In brief, certified calibration solutions are prepared by gravimetric methods from analytical standards whose purity (Section 2.2.1) has been assessed by at least two... 

However, in many cases the analyst is faced with the task of quantitative analysis for an analyte for which a certified calibration solution is not available, or is too expensive and thus inappropriate for the stated purpose for which the analysis is to be conducted. In such cases it is necessary to prepare the calibration solutions from scratch from an analytical standard. Precautions in weighing the analytical standard are discussed in Section 2.3.3, and preparation of stock and spiking solutions in Section 9.5.4. 

The requirements for a Certificate of Analysis (COA) were described in Section 2.2.2, with emphasis on matrix CRMs rather than analytical standards, so some of these requirements are not applicable in this case. The crucial parameters for an analytical standard, apart from names and addresses of the certifying body and its certifying officers, material code and batch numbers, hazard warnings, date of certification and expiry date etc., are purity (both chemical and chiral if relevant, Section 2.2.1) and moisture (and possibly inorganic salt or residual solvent) content, and stability information. 

Mean value control cards, however, do not indicate any errors related to the sample matrix. It is possible to check the analytical process for matrix influences by determination of the recovery rate, although it only determines matrix-related, proportional systematic deviations. Constant systematic deviations remain undiscovered. Thus, the determination of the recovery rate is only a limited measure for controlling accuracy. If certified reference standards are used, the target value (Xget) is known. Together with the measuring value x eas, the recovery rate can be determined according to ... 

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