System suitability precision

For shock-synthesis and processing experiments, less precise systems are typically employed. These systems use commercial explosives that may be used to accelerate plates or to compress samples in the form of a tube. These systems are suitable for establishing nominal shock conditions for materials processing experiments, but are generally not suitable for careful characterization of materials response [87G02, 88M01]. 

Of all the requirements that have to be fulfilled by a manufacturer, starting with responsibilities and reporting relationships, warehousing practices, service contract policies, airhandUng equipment, etc., only a few of those will be touched upon here that directly relate to the analytical laboratory. Key phrases are underlined or are in italics Acceptance Criteria, Accuracy, Baseline, Calibration, Concentration range. Control samples. Data Clean-Up, Deviation, Error propagation. Error recovery. Interference, Linearity, Noise, Numerical artifact. Precision, Recovery, Reliability, Repeatability, Reproducibility, Ruggedness, Selectivity, Specifications, System Suitability, Validation. 

In the new Stratus CS system results are available in less than 15 min after sample draw and the system has the capability to analyze four samples in less than 30 min. Ease of use, analytical sensitivity, accuracy, precision, and reproducibility makes this system suitable for use in chest pain centers, emergency departments, critical care units, observation wards and clinical laboratories. 

Once the appropriate dissolution conditions have been established, the method should be validated for linearity, accuracy, precision, specificity, and robustness/ruggedness. This section will discuss these parameters only in relation to issues unique to dissolution testing. All dissolution testing must be performed on a calibrated dissolution apparatus meeting the mechanical and system suitability standards specified in the appropriate compendia. 

The CE method was validated in terms of accuracy, precision, linearity, range, limit of detection, limit of quantitation, specificity, system suitability, and robustness. Improved reproducibility of the CZE method was obtained using area normalization to determine the purity and levels of potential impurities and degradation products of IB-367 drug substance. The internal standard compensated mainly for injection variability. Through the use of the internal standard, selected for its close mobility to IB-367, the method achieved reproducibility in relative migration time of 0.13% relative standard deviation (RSD), and relative peak area of 2.75% RSD. 

To validate the suitability of methods, experiments to establish specificity, accuracy, precision, limits of detection, limits of quantitation, linearity, range, and robustness should be conducted. Furthermore, appropriate system suitability criteria should be developed to assure that the method is performing to pre-established criteria at the time of use. 

Further discussion of method validation can be found in Chapter 7. However, it should be noted from Table 11 that it is frequently desirable to perform validation experiments beyond ICH requirements. While ICH addresses specificity, accuracy, precision, detection limit, quantitation limit, linearity, and range, we have found it useful to additionally examine stability of solutions, reporting threshold, robustness (as detailed above), filtration, relative response factors (RRF), system suitability tests, and where applicable method comparison tests. 

ISO defines validation as Conformation by examination and provision of objective evidence that the particular requirements for a specified intended use are fulfilled. This is decided by using a number of performance characteristics. These are specificity, linearity, range, accuracy, precision, detection limit (DL), quantitation limit (QL), and robusmess. System suitability testing (SST) is an integral part of many analytical procedures. Definitions of these terms based on the recommendations of the ICH Guideline Q2 (Rl) are given in Table... 

System suitability tests for chromatographic impurities procedures, such as precision, resolution factor, calibration standard, and tailing factor, should be considered as appropriate. In the presence of multiple peaks, a resolution factor between the two closest peaks should be proposed. For reliable quantitation, baseline resolution of the impurities will provide accurate measurement of the... 

System suitability should be based on criteria and parameters collected as a group that will be able to define the performance of the system. Some of the common parameters used include precision of repetitive injections (usually five or six), resolution (R), tailing factor (T), number of theoretical plates (N), and capacity factor ( ). 

The method was found to be deficient in some areas, such as precision and system suitability. This is especially important as the analytical laboratory gets more experience and more information as to the degradation profile of the sample as it progresses toward submission. If a new impurity is found that makes the method deficient, this method will need to be revalidated. 

Control sample a representative batch of drug substance (or drug product). Typically, control samples are tested in all analyses to ensure consistency in method performance across different runs. Sometimes, they are used as part of the system suitability test to establish the run-to-run precision (e.g., intermediate precision, reproducibility). 

System Suitability Tests. The appropriate system suitability tests should be defined before method validation (e.g., precision, resolution of critical related substances, tailing, detector sensitivity). These system suitability tests should be performed in each method validation experiments. System suitability results from the method validation experiment can be used to determine the appropriate system suitability acceptance criteria. 

Fit the purpose calibration. It is common sense to check instrument performance each day, and GLP requirements simply formalize the performance and documentation of these checks. On the other hand, it is also important to use the right test (full calibration, verification, system suitability test, or instrument and method validation) to verify the performance and to avoid needlessly lengthy procedures. As already discussed (see Sections 13.2.3 and 13.3.1), it is not always necessary to perform a MS full calibration every day. For example, if a particular MS is used only to record complete full-scan mass spectra, a daily calibration or verification of the calibration of the m/z ratio scale is required. However, in the case where a MS is coupled with an LC and utilized primarily for the analysis of one or more analytes in the selected ion monitoring (SIM) mode, it does not always require a daily verification of the calibration. In this specific case it is quite common in LC-MS and LC-MS/MS applications to test only the following performance parameters (a) sensitivity, (b) system precision,... 

Piezoelectric hygrometers (Fig. 6.S6) These consist of a quartz crystal with a hygroscopic coating (Fig. 6.S60 and Section 6.3.3). Two crystals are usually employed and the wet gas (sample) and dry gas (reference) are passed over them alternately (normally every 30s—Fig. 6.566). The crystals absorb and desorb. The difference in angular frequency Am is proportional to the concentration of water vapour by volume. Capable of high precision. Can monitor moisture contents of the order of 1 to 3000 ppm by volume. Usually measures up to dewpoint of 310 K. Fast response but expensive. Sample must be dean to avoid contamination of the crystals. Complex sampling system. Suitable for on-line use. 

It should be pointed out here that the surface free energy at a given temperature and surface energy (or enthalpy) for a solid system, as seen in Eq. (24), may be measured precisely from suitable experiments discussed in the next sections [70]. 

System suitability parameters with their respective acceptance criteria should be a requirement for any method. This will provide an added level of confidence that the correct mobile phase, temperature, flow rate, and column were used and will ensure the system performance (pump and detector). This usually includes (at a minimum) a requirement for injection precision, sensitivity, standard accuracy (if for an assay method), and retention time of the target analyte. Sometimes, a resolution requirement is added for a critical pair, along with criteria for efficiency and tailing factor (especially if a known impurity elutes on the tail of the target analyte). This is added to ensure that the column performance is adequate to achieve the desired separation. 

Figure 7.8 Rationale for recommended system suitability test. A, linear, negligible intercept, response = y jxx = 2/ 2 = > 3/ 3 yijXA (therefore RSD on response measured at ditferent analyte concentrations should not be significantly higher than the precision of the assay based on the concentration at mid-point of linearity range provided the different concentrations are not too far from the mid-point) A, linear, non-zero intercept, y l/x i y llx 2 A y ilx i A A", non-linear, zero intercept, A 4= fAlx A.

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