Method validation high-level linearity

Typically, linearity and accuracy determination covers a wide concentration range (e.g., 50% of the ICH reporting limit to 150% of specification). However, the concentration range for precision will be limited by the availability of sample of different related substance levels. Therefore, to ensure an appropriate method validation range with respect to precision, it is critical to use samples of low and high levels of related substance in precision experiments (e.g., fresh and stressed samples). 

Principles and Characteristics Whereas parameters most relevant to method development are considered to be accuracy, system precision, linearity, range, LOD, LOQ, sensitivity and robustness, method validation parameters are mainly bias, specificity, recovery (and stability of the analyte), repeatability, intermediate precision, reproducibility and ruggedness. However, method development and validation are highly related. Also, validation characteristics are not independent they influence each other. Acceptance criteria for validation parameters should be based on the specification limits of the test procedure. Quantitation and detection limits need a statement of the precision at their concentration levels. Procedures used for validation of qualitative methods are generally less involved than those for quantitative analytical methods. According to Riley [82], who has discussed the various parameters for validation of quantitative analytical methods, the primary statistical parameters that validate an analytical method are accuracy and precision. 

In a general way, validation is the documentary evidence process that an analytic method will lead, with a high degree of security, to obtain precise and accurate results, within specifications and quality attributes previously established. Validation data must be submitted for all analytes included in the residue definition for all representative sample matrices to be analyzed at adequate concentration levels. The five fundamental parameters required for the European Commission for analytic validations of methods used with pesticides are as follows linearity and range, accuracy, precision, selectivity, and LOD and LOQ. These are collected in the SANCO guidelines together with their well-detailed requirements [43 5]. 

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