Stability studies sample analysis

Hence, it is important to ensure that sufficient validation/QC samples are prepared to cover all of the expected validation batches and, if possible, the study sample analysis batches also. For commercial QC material, this means obtaining sufficient material from the same manufacturer s lot number. Clearly, stability or shelf life may limit how long this material may be stored and used. 

For study sample analysis the calibration curve and QC samples are evaluated separately, and run acceptance is based upon criteria estabhshed for both curves and QCs. For validation runs, however, only the standard curve and other factors such as carryover are considered for run acceptance and aU of the results for the various types of validation QCs, e.g., precision and accuracy, stability, etc., are reported and used for statistical analysis. It is important at this time to emphasize the distinction between a failed and rejected validation run. Runs may be rejected for specific assignable cause such as documented evidence that the method was run incorrectly or hardware failure (Section 10.5.2c). Data from failed runs on the other hand, such as those where an excessive number of calibrators are considered to be outhers or QCs used to assess precision and accuracy do not meet the... 

Postpreparative Stability (Autosampler Stability) Stability of processed samples should be determined at the autosampler temperature that will be used during study sample analysis and for a duration of time equal to or greater than the batch size expected to be used for routine study sample analyses. If sample extracts are to be stored (e.g., in a refrigerator or freezer) before analysis, then the stability of the analyte in the reconstituted sample extract under these conditions should be investigated. In postpreparative stability assessment, the mean concentration value obtained from each QC concentration level after storage in autosampler is compared with the respective nominal concentration value. The mean bias (%) between the values should be within +15%. If the stability is demonstrated, then an LC-MS/MS run can be restarted after an unexpected interruption as long as system suitability has been established and documented. 

In many cases, there is difficulty in preserving residues in samples after collection and prior to pesticide analysis which coincides with a rapid further degradation and mineralization of the pesticide residues under most environmental conditions. Storage stability studies and studies on the reactivity of sample collection equipment in addition to field quality assurance procedures can help address some of these questions. Concerns are accentuated for compounds that have short half-lives in the environment but still have high acute toxicity. 

The validation process begun in Phase I is extended during Phase II. In this phase, selectivity is investigated using various batches of drugs, available impurities, excipients, and samples from stability studies. Accuracy should be determined using at least three levels of concentration, and the intermediate precision and the quantitation limit should be tested. For quality assurance evaluation of the analysis results, control charts can be used, such as the Shewart-charts, the R-charts, or the Cusum-charts. In this phase, the analytical method is refined for routine use. 

From the discussion presented of reactions in solids, it should be apparent that it is not practical in most cases to determine the concentration of some species during a kinetic study. In fact, it may be necessary to perform the analysis in a continuous way as the sample reacts with no separation necessary or even possible. Experimental methods that allow measurement of the progress of the reaction, especially as the temperature is increased, are particularly valuable. Two such techniques are thermo-gravimetric analysis (TGA) and differential scanning calorimetry (DSC). These techniques have become widely used to characterize solids, determine thermal stability, study phase changes, and so forth. Because they are so versatile in studies on solids, these techniques will be described briefly. 

Because a great deal of the characterization knowledge resides in the analytical laboratory, this is where most stability and formulation work occurs. It is not unusual for the bioanalytical laboratory to be involved in the support of clinical studies (i.e., patient sample analysis). 

A critical study of reference standards for residue analysis of chloramphenicol in meat and milk was also carried out using a radioimmunoassay and gas chromatography (GC) equipped with electron capture and mass detectors (41). Although the concentration of chloramphenicol was only 1 ppb in milk and 10 ppb in meat, approximately 70% of the antibiotic could be recovered by the assay. A stability study of chloramphenicol in milk samples stored at 30 to 80 C showed that stability decreases with increasing drug concentration when the sample is stored at 30 C. 

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