Selectivity and Specificity

In the common vernacular, the terms specificity and selectivity are often interchangeably used. More properly, a method is said to be specific if it provides a response for only a single analyte, while the term selective means that the method provides responses for a number of chemical entities that may be distinguished from each other. Selectivity also implies the ability to separate the analyte from degradation products, metabolites, and coadministrated drugs [12]. USP 28 [1] defines specificity as the ability to assess the analyte unequivocally in the presence of other components such as impurities, degradation products, and the matrix. IUPAC and AOAC have preferred the use of the term selectivity than specificity for methods that are completely selective, while USP, ICH, and FDA used the term specificity . Due to the very number of limited methods that respond to only one analyte, the term selectivity is usually more suitable, and this usage will be used in this work. 

In chromatography techniques, selectivity can be proved by the existence of good separation between the analyte and the other components (such as the matrix, impurities, degradation product(s), and metabolites). A consequence of this requirement is that the resolution of the analyte from the other components should be more than 1.5-2.0. In order to detect the possibility of coelution of other substance(s), the purity of the analyte peak should also be determined. For instance, the UV-Vis spectrum of the analyte peak/spot can be used to determine 4the purity of the analyte peak/spot, in this case the correlation coefficient V (this term is used by the software of DAD System Manager Hitachi, and CATS from Camag). With the same meaning and mathematical equation, other terms are used, such as Match 

Factor MF (Agilent ChemStation), or Similarity Index SI (Shimadzu Class-VP, Chromatography Data System or Shimadzu/LCsolution). 

A representative example of this process is shown in Fig. 2. The spectra of the analyte peaks can be measured at the upslope, the top, and at the downslope, or the whole spectrum of the chromatography peak can be compared. In the latter case, the term totalpeak purity is used, and a purity curve of the peak can also be recorded. These operations can be performed by a HPLC system equipped with a DAD detector [13], or for TLC a densitometer that can measure the UV-Vis spectrum of the analyte spot should be used. If the value of the purity is 0.000 0.8900, it is not pure, and a purity of 0.9000-0.9500 means that the peak is contaminated (Shimadzu Class-VP, Chromatography Data System). 

For determining peak identity, the whole spectral data of the standard and the analyte should be compared, and the value of r or MF or SI can be calculated using the software of the HPLC/densitometer equipment as described above. 

The three single sensitivities can be found at the diagonal of the matrix S(i). The total multicomponent sensitivity according to Eq. (7.18) is Stotai = 90 au3/(mol/L)3. 

In such a well-defined analytical system the term selectivity is relevant to multicomponent analysis. Selectivity of an analytical procedure characterizes the extent to which n given analytes can be measured simultaneously by n sensors (detecting channels) without interferences by other components 

On the other hand, specificity refers to single component analysis and means that the one individual analyte can be undisturbedly measured in a real sample by a specific reagent, a particular sensor or a comparable measuring system (e.g., measurement of emitted or absorbed radiation at a fixed wavelength). 

Selectivity and specificity are important performance characteristics of analytical procedures, especially in connection with validation processes. Nevertheless, both terms are used mostly verbal and a quantification is avoided, as a rule (IUPAC see Vessman et al. [2001]). Moreover, the concepts of selectivity and specificity are used interchangeably and synonymously. Occasionally, specificity is regarded as an intensification of selectivity, viz. the ultimate of selectivity (den Boef and Hulanicki [1983] Persson and Vessman [1998, 2001] Prichard et al. [2001]). 

A clear differentiation between selectivity and specificity was firstly given by Kaiser [1972] together with a quantification of the both characteristics. According to him an analytical procedure is known as selective if it can detect and determine simultaneously several components independently from each other. On the other hand, a procedure is known as specific if only one species can be detected and determined independently from all the other components which are present in the sample but does not contribute to the signal in this case. 

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Tandem mass spectrometry (MS/MS) produces precise structural or sequence information by selective and specific induced fragmentation on samples up to several thousand Daltons. For samples of greater molecular mass than this, an enzyme digest will usually produce several peptides of molecular mass suitable for sequencing by mass spectrometry. The smaller sequences can be used to deduce the sequence of the whole protein. 

Brown, Royce N., Selection and Specification of Process Compressors, in ASME 36th Petroleum Division Conference Publication, Enhanced Recovery and Rotating Equipment—A Workbook for Petroleum Engineers, New York American Society of Mechanical Engineers, 1980, pp. 57-64,... 

The concepts of the National Electrical Code (NEC) gronps and the Maxi-mnm Experimental Safe Gap (MESG) are important criteria in the selection and specification of dry type flame arresters. These are explained below. 

Determine proper pump selection and specifications when pumping oil with SpGr of 0.9 and viscosity of 25 cen-tipoise at the pumping temperature, if the pump must deliver 125 GPM at 86 feet total head (calculated using the viscous liquid). 

Application, Selection and Specification, Cat. 7387-1, 1988, Fike Metal Products Co. 

In the past, USA competing companies could not cooperate, such as in R D, without breaching antitrust laws. Patent pooling, such as collecting and cross-licensing patents, was precluded. Today the antitrust laws are reviewed, interpreted, and enforced less stringently, which permits industrial cooperation in selected and specific areas where poling does exist. This explanation is a simplistic summation to a very complicated situation. 

The general, selective and specific formation of complexes by metallic cations. G. Schwarzenbaeh, Adv. Inorg. Chem. Radiochem., 1961, 3, 257-285 (70). 

After extraction, each phase may be studied independently in order to obtain a useful qualitative evaluation of the components in the original sample. The selectivity and specificity of fluorescence analysis can be especially beneficial in identification of PAHs. For example, some components could be identified by examining the fluorescence spectra of the organic and aqueous phases. Characteristic peak shapes may reveal identities of the components. For more complicated systems in which the spectra overlap, lifetime measurements may be used to identify components (27). 

Appropriately designed biophysical studies can elucidate the mode(s), the binding affinities and the nature of the ligand-nucleic acid interaction that give rise to the observed selectivity and specificities. Thus, it is worthwhile to describe briefly the various physical techniques used to study alkaloid-DNA/RNA interactions. 

Merrick, R. C. (1990) Valve Selection and Specification Guide (Spon.). 

Danzer K (2001) Selectivity and specificity in analytical chemistry. General considerations and attempt of a definition and quantification. Fresenius J Anal Chem 369 397... 

Fig. 7.6. Selectivity matrix (a) and specificity vector of the detecting channel A (b) with the simplified formulas (all the xt and xj = 1) for selectivity and specificity (on the right)...

The problem is illustrated in a simplified way in Fig. 7.6. The quantities sel(A,B,..., N) and spec(A,B,..., N) not only define absolute characteristics but also a certain degree of selectivity and specificity of an analytical procedure. The measures can take values from 1 for fully selective or totally specific procedures, respectively. The range of selectivity R sel and the range of specificity R spec are given by... 

For practical purposes, it can be supposed that values of set > 0.9 and spec > 0.9 indicate fair selectivity and specificity, respectively, whereas smaller values show more and more insufficient selectivity and specificity. 

Table 7.3. Selectivities and specificities in case of various sensitivity matrixes... 

The concept of selectivity and specificity has been applied to characterize interferences appearing in two different ICP-MS techniques (Horn [2000]). Classical ICP-MS with pneumatic nebulization and ETV-ICP-MS are compared for the determination of traces of zinc in sea-water. Whereas spectral interferences decrease using the ETV device, nonspectral interferences increase significantly (Bjorn et al. [1998]). A quantitative comparison of the both analytical procedures, here called PN (pneumatic nebulization) and ETV (electrothermal vaporization, Sturgeon and Lam [1999]) is possible by means the specificity as a function of the Zn concentration (Horn [2000]). The spectral interferences on the four zinc isotopes are listed in Table 7.4. 

As expected, the concept of selectivity and specificity is closely related to that of sensitivity. The same may be anticipated for the concept of robustness and ruggedness. 

Davis, P.D., and Crapps, E.C. (2006) Selective and specific preparation of discrete PEG compounds. US Patent Application Publication No. 2006/0020134. 

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