Quantitative risk analysis, validity

In practical applications, dispersion calculations need to be performed in topographically complex environment. Thus, solid obstacles intervening in the area dispersion should be counting in the computations. In previous validation works, it has been proved that CFD codes constitute powerful tools for complex terrain dispersion simulation providing high accuracy results with excellent visualization capabilities, which can be helpful in quantitative risk analysis applications [55]. The dominating mixing mechanism between... 

The analysis of this principal scheme of ERA is so defined that the quantitative risk assessment is valid only when based on a complete operational flowchart. 

In the course of assessing your company s current PSM status, you and your team have almost certainly gained a clear sense of which facilities pose the greatest risk, whether by virtue of inherent process hazards, human factors, management systems, or a combination. As you set priorities for implementation you should closely review information gleaned from the assessment tasks. In addition, you should try to validate or flesh out your impressions through some more quantitative analysis that can help to identify priority facilities. 

Although the lower limit of quantitation is established during assay validation and prior to microdosing, assay sensitivity remains an uncertainty until the actual analysis of the microdose samples as well. There is always the danger that plasma exposures from the microdose are lower than predicted and as a result plasma concentrations from some or all of the time points cannot be detected by the LC-MS/MS method. Reduction of this risk is achieved by collaborative communication between the bioanalytical chemist and the project team. Conservative estimates on bioavailability and clearance can be used to establish the necessary limit of detection needed to determine plasma concentrations for all time points. Updates on the progress of the assay development allow the team to decide if the achievable limit of detection will enable the determination of plasma concentrations from enough time points to make a go-no go decision. Of course, sensitivity is not an issue with AMS, which practically ensures that plasma concentrations will be determined, possibly for several days, enabling the observation of complex PK and clearance from deep compartments. 

Sample preparation in NLC and NCE is the most important step in analysis due to the nano nature of these modalities. The sampling should be carried out in such a way as to avoid changes in the chemical composition of the sample. The quantitative values of species depend on the strategy adopted in sample preparation. Extraction recoveries may vary from one species to another and they should, consequently, be assessed independently for each compound as well as for the compounds together. Materials with an integral analyte, that is, bound to the matrix in the same way as the unknown, which is preferably labeled (radioactive labeling) would be necessary, which is called method validation. As discussed above few papers described off- and online sample preparation methods on microfluidic devices. Of course, online methods are superior due to lower risk of contamination and error of methods. Not much work been carried out on online nanosample preparation devices, which need more research. Briefly, to get maximum extraction of analytes, sample preparation should be handled very carefully. 

---