Sampling stability studies

The assistance of Maria Risholm-Sundman in performing some of the sample-stability studies is gratefully acknowledged. 

The stability of working sample solutions is assessed under ambient conditions. The analyst should verify the stability of the sample received from the process chemist or plant to determine if any special handling procedures are required. The impact of the sample preparation delay on the IPC preparation should also be evaluated. The length of the sample stability study will be defined by process requirements. 

The measurement method used for the homogeneity study should have a very good repeatability. For a stability study, where often samples are measured at different days, the reproducibility of the measurement method is of primary importance. 

Stability Assessment In general there is no formal stability study prior to the certification of a natural matrix S RM. H owever, the stability of the certified analytes is monitored on a regular basis, typically every 1-3 years depending on the analytes, as the SRMs are analyzed as control samples during the analyses of similar matrix samples. A recent study of PAHs in frozen mussel tissue over nearly 10 years found no significant changes in the concentrations of the measured PAHs (Schantz et al. 2000). 

Storage stability studies for carfentrazone-ethyl compounds on crop matrices have shown a pattern of stability for at least 7-24 months, depending on the study program or the maximum sample storage interval for the study. Carfentrazone-ethyl was not stable in field corn starch, potato tuber and bovine kidney. The residue results indicated that a significant portion of carfentrazone-ethyl was converted to C-Cl-PAc in these matrices however, the total amount of carfentrazone-ethyl and C-Cl-PAc accounted for the original spiking level. Since both carfentrazone-ethyl and C-Cl-PAc were determined in these stability studies, the instability of carfentrazone-ethyl was not of any concern. 

Storage stability studies for sulfentrazone compounds on crop matrices showed a pattern of stability for at least 3-38 months, depending on the study program or the maximum sample storage interval for the study. 

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 degradation of agrochemicals during storage may result from a variety of factors such as acidic and alkaline hydrolysis, enzymatic action, etc. It is recommended that a preliminary stability study be performed for the chemical in the environmental sample. If the chemical is stable under acidic conditions, for example, samples can be stored after acidification with hydrochloric or phosphoric acid. 

Validate routine methods, i.e., define the conditions under which the assay results are meaningful.115 To do that, one must select samples that are truly representative of the product stream. This may be a difficult task when the process is still under development and the product stream variable. The linearity of detector response should be defined over a range much broader than that expected to be encountered. Interference from the sample matrix and bias from analyte loss in preparation or separation often can be inferred from studies of linearity. Explicit detection or quantitation limits should be established. The precision (run-to-run repeatability) and accuracy (comparison with known standards) can be estimated with standards. Sample stability should be explored and storage conditions defined. 

Monsanto. 1981. Stability study of natural sediments samples preserved by frozen storage with attachment. Monsanto Company, St. Louis, MO. 

Moreover, it is also possible to detect minor degradation products in the sample by XPS and this makes the method also interesting when performing stability studies. For instance, it is possible to detect the final degradation product polyenes in PVC by means of XPS [89,90], which are usually present in very minor concentrations (ppb and below). However, especially for the detection of polyenes, Raman spectroscopy is a very simple and powerful method, and might therefore be the method of choice in such cases. 

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. 

Any decision to establish automated or robotic systems must carefully consider prerequisites such as the annual numbers of samples to be processed to achieve an acceptable cost-to-benefit ratio. Late phase development stability studies may benefit from fully automated systems based on the enormous numbers of samples to be analyzed for each stability time point. The use of automated systems in manufacturing quality control is now required due to the sheer number of samples to be... 

In addition to the direct absorbance methods, colorimetric methods are suited for relatively pure proteins as purification progresses. They are accurate if calibrated from a standard curve of the test protein reference sample and fast if automated. However, they are not as simple to perform as direct absorbance methods. Hence they are not as suitable for production as direct absorbance methods. The relative simplicity of colorimetric methods makes them more suited to automated formulation and stability studies and total-protein assays of complex mixtures. Microtiter plate versions of colorimetric assays allow for automation and consumption of relatively small sample sizes while requiring little specialized equipment or training. 

For those scientists who had to perform quantitation, the linearity of the A/D was also critical. Linearity is the condition in which the detector s response is directly proportional to the concentration or amount of a component over a specified range of component concentrations or amounts. It is imperative that the A/D not add any additional error or variability to the performance of the detector. The resulting calibration curve now becomes dependent on the combined linearity of the detector and the /VD. Accurate quantitation requires that the system is linear over the range of actual sample concentrations or amounts. Many pharmaceutical assays, like degradation and stability studies, require that the system be able to identify and quantitate very disparate levels of peaks. In many cases, this translates into a 3 to 4 order of magnitude difference between the main active component and the impurities that need to be quantitated. 

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