Analytical procedure system suitability test

The validation of an analytical procedure produces performance parameters of a well-behaved and well-conditioned system/instrument (including defined variations) which are more or less snapshots of the combination procedure/system. In order to routinely confirm the suitability of the integrated measurement instrumentation used with a given procedure, system suitability test parameters should be defined on the basis of the validation results and robustness studies. Larger variations under routine conditions or multiple laboratories should also be taken into consideration. 

The procedure known as system suitability test consists in testing an instrumental analytical system against documented performance specifications for a given analytical method. System suitability tests are based on the concept that the equipment, electronics, analytical operations and samples constitute an integral system that can be evaluated as a whole. These tests are used to make sure that the resolution and reproducibility of the system are adequate for... 

Each analytical procedure should include the appropriate system suitability tests defining the critical characteristics of that system. Other parameters may be included at the discretion of the applicant. 

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... 

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,... 

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 " " ... 

Very recently (Briscoe 2007) the question of system suitability testing for LC-MS/MS applications in biomedical analysis was addressed in detail, and a generic test that monitors instrument performance throughout an analytical run was described. This procedure includes tests for signal stability, carryover and instrument response in a fashion that is integrated throughout an analytical run of multiple samples. The importance of this work is illustrated by... 

The evaluation of robustness should be considered in the development of the assay and will depend on the type of procedure under development. It must show the reliability of a method with respect to deliberate variations in method parameters. If measurements are susceptible to variations in analytical conditions, the analytical conditions should be suitably controlled or a precautionary statement might be included in the procedure. One consequence of the evaluation of robustness may be that a series of system suitability parameters is established to ensure that the validity of the analytical procedure is maintained whenever used. Typical parameters to be tested would be the following sample concentration, sample stability, labeling variability (if applicable), injection variability, reagent lot-to-lot variability, and capillary vendor. 

If analytical measurements are susceptible to variations in the analysis parameters or sample preparation conditions, the method must be suitably controlled or a precautionary statement must be included in the written procedure that alerts the chemist to the susceptibility. The method s system suitability parameters should be defined in such a way that meeting all system suitability criteria would ensure that the method is currently being performed within the acceptance window provided by validation robustness testing. 

Prior to performing a formal validation, the analytical chemist should have performed some prevalidation during method development. The expectation is that a well-developed HPLC method should subsequently be validated with no major surprises or failures. Prior to validation, specificity and some degree of robustness should be demonstrated. In addition, some form of system suitability criteria will have been established. System suitability evaluates the capability of an HPLC system to perform a specific procedure on a given day. It is a quality check to ensure that the system functions as expected and that the generated data will be reliable. Only if the system passes this test should the analyst proceed to perform the specific analysis. System suitability can be based on resolution of two specified components, relative standard deviation, tailing factor, limit of quantitation or detection, expected retention times, number of theoretical plates, or a reference check. 

The various levels of precision may be calculated by means of an analysis of variances.The overall variation is divided into the contributions within and between the series, allowing us to assess the most sensitive part of the analytical procedure as well as the robustness (Table 4). Acceptance limits for assay determinations can be derived from specification limits established on the basis of experience and the analytical state of the art. With the former approach, the suitability of either the specification limits or the precision of the analytical procedure is tested. Typical RSDs for system precision of LC assay procedures should range below 1%, for repeatabilities up to 1-2%, and for intermediate precision/reproducibility twice the value for the (average) repeatability can be expected (depending on the amount of variations, time period, etc.). For impurity determinations, the... 

Every in vitro method should be detailed in the developer laboratories using Standard Operating Procedures (SOPs) covering all essential components and steps of the method. The SOP(s) should be sufficiently defined and described and should include the rationale for the test method, a description of the materials needed, such as specific cell types, a description of what is measured and how it is measured, a description of how data will be analyzed, acceptance and decision criteria for evaluation of data, and what are the criteria for suitable test performance. All limitations, e.g., lack of metabolic competences (presence of phase 1 and phase 2 biotransformation activities) or absence of critical transporters, should be included in the in vitro method description. In general, the in vitro method should not require equipment or material from a unique source. This may not be always possible for particular in vitro test systems or other components of the method in which case a license agreement between the provider and a recipient/user may be required. For complex and/or specialized equipment, the equipment specifications and requirements should also be described. Acceptance criteria for measurements carried out on the equipment should also be provided where applicable (e.g., for analytical endpoint determinations, linearity and limits of detection should de detailed) [2],... 

The life scientist interested in the concentration, distribution and speciation of chromium in biological systems is in need of reliable and precise analytical data. These can only be obtained by applying first of all a representative sampling and handling procedure, followed by the correct use of an analytical technique with suitable sensitivity. Finally, the bias of the whole method can be tested by analyzing biological standard reference materials, certified for chromium at comparable levels as the unknowns. 

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