Method performance terms sensitivity

Biopolymers are employed in many immunological techniques, including the analysis of food, clinical samples, pesticides, and in other areas of analytical chemistry. Immunoassays (qv) are specific, sensitive, relatively easy to perform, and usually inexpensive. For repetitive analyses, immunoassays compare very favorably with many conventional methods in terms of both sensitivity and limits of detection. 

The terms defined above are all important in the consideration of the overall performance of an analytical method. The greatest sensitivity (response) does not necessarily imply the lowest limit of detec-tion/determination as a more intense signal may also be observed from... 

The terms detective and detectivity rather than the frequently (mis)used terms sensitive and sensitivity, are used to denote analyte detection capability of the method. For a given method, although usually higher sensitivity (slope of calibration curve) is synonymous with greater detectivity, (lower detection limit), this is not invariably so, and the latter is the more accurate term. In addition, for performance comparisons among different methodologies, sensitivities cannot usually be compared due to the typically different response units inherent in the methods comparisons, however, of detectivities, if expressed as, e.g., mg of analyte kg-1 of sample, can be made. 

As a compound proceeds into first-in-human clinical trials, the assay method reaches an apex in terms of performance. These methods require maximal sensitivity to be able to support dose escalation studies. The selectivity of the method is well established versus matrix components, concomitant medications, and metabolites. The assay is revalidated in the human matrices (plasma, serum, and urine) and will again meet well-established guidelines for inter- and intraday precision and accuracy. If significant changes are made to the method, a comparison of methods study will be conducted to understand the relative accuracy of the methods. After this benchmark, assay requirements, especially limit of quantitation, are usually less demanding and use of the assay becomes more routine, as it is applied again and again to additional clinical studies for pharmacokinetic support. 

Method Performance Detection Limits One common way of assessing one aspect of method performance is by detection limit, or by the term detectivity (power to detect the analyte), as opposed to the term sensitivity (strictly the slope of the calibration function), as used in the past by this author (Ihnat 1984). The concept of detection limit is defined and discussed in books on analytical chemistry and in papers by analysts and committees delving into the mathematical, statistical and quality facets of analytical method performance. Basically it is the amount, absolute (mass) or relative (mass/volume or mass/mass,... 

These requirements, along with other recommendations found in the guidance documents available, constitute the fitness-for-purpose requirements for residue methods using mass spectral detection. An excellent discussion of some issues related to the performance of mass spectrometry methods is contained in a 2010 paper, including the misuse of the term sensitivity and the challenges of establishing lower limits for the routine application of mass spectrometric methods. ... 

Method performance in air analysis involves terms such as accuracy, storage stability, capacity, sampling rate, recovery, and sensitivity. To evaluate the performance of a developed method, certified reference materials for particulate matter, such as urban dust SRM 1649a particulate matter from NIST (Gaithersburg, MD, USA) can be purchased. In addition, a standard reference material has been recently developed for the determination of organic compounds in house dust the SRM 2585 is intended for using in method validation for the analysis of PAHs, PCBs, chlorinated pesticides, and PBDEs (Poster et al. 2007). 

Stage that requires high efficiency as well as speed, due to the complexity of the sample matrix, and hence it is particularly challenging to achieve the goals. Therefore, the development of a rapid, sensitive, and reproducible method has been required for separation and determination of capsaicinoid compounds. The addition of ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method fulfilled these aforementioned demands and showed some complementary advantages to the conventional HPLC-MS, u-HPLC methods in terms of shorter analysis times, low sample volume, and much improved sensitivity [71]. Therefore, nowadays this UPLC-MS technique is routinely performed in pharmaceutical industries and related contract research institutes, laboratories concerned with biochemistry, biotechnology, environmental analysis, natural product research, and several other research fields. The UPLC-MS method has successfully been applied for the determination of n-DHC, C, DHC, h-C, and h-DHC present in the varieties of hot peppers [71]. 

In the last twenty years, various non-deterministic methods have been developed to deal with optimum design under environmental uncertainties. These methods can be classified into two main branches, namely reliability-based methods and robust-based methods. The reliability methods, based on the known probabiUty distribution of the random parameters, estimate the probability distribution of the system s response, and are predominantly used for risk analysis by computing the probability of system failure. However, variation is not minimized in reliability approaches (Siddall, 1984) because they concentrate on rare events at the tail of the probability distribution (Doltsinis and Kang, 2004). The robust design methods are commonly based on multiobjective minimization problems. The are commonly indicated as Multiple Objective Robust Optimization (MORO) and find a set of optimal solutions that optimise a performance index in terms of mean value and, at the same time, minimize its resulting dispersion due to input parameters uncertainty. The final solution is less sensitive to the parameters variation but eventually maintains feasibility with regards probabilistic constraints. This is achieved by the optimization of the design vector in order to make the performance minimally sensitive to the various causes of variation. 

The intensive mixers mentioned above are illustrated in Figure 9.3, together with others proposed in the literature in general they have been well characterized in terms of internal hydrodynamics and mixing performances, either by flow visualization techniques or using chemical methods, by mixing sensitive competitive reaction schemes computational fluid dynamics also supplied much information. 

If analytical methods are validated in inter-laboratory validation studies, documentation should follow the requirements of the harmonized protocol of lUPAC. " However, multi-matrix/multi-residue methods are applicable to hundreds of pesticides in dozens of commodities and have to be validated at several concentration levels. Any complete documentation of validation results is impossible in that case. Some performance characteristics, e.g., the specificity of analyte detection, an appropriate calibration range and sufficient detection sensitivity, are prerequisites for the determination of acceptable trueness and precision and their publication is less important. The LOD and LOQ depend on special instmmentation, analysts involved, time, batches of chemicals, etc., and cannot easily be reproduced. Therefore, these characteristics are less important. A practical, frequently applied alternative is the publication only of trueness (most often in terms of recovery) and precision for each analyte at each level. No consensus seems to exist as to whether these analyte-parameter sets should be documented, e.g., separately for each commodity or accumulated for all experiments done with the same analyte. In the latter case, the applicability of methods with regard to commodities can be documented in separate tables without performance characteristics. 

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