Quality control sample stability

Analytical measurements should be made with properly tested and documented procedures. These procedures should utilise controls and calibration steps to minimise random and systematic errors. There are basically two types of controls (a) those used to determine whether or not an analytical procedure is in statistical control, and (b) those used to determine whether or not an analyte of interest is present in a studied population but not in a similar control population. The purpose of calibration is to minimise bias in the measurement process. Calibration or standardisation critically depends upon the quality of the chemicals in the standard solutions and the care exercised in their preparation. Another important factor is the stability of these standards once they are prepared. Calibration check standards should be freshly prepared frequently, depending on their stability (Keith, 1991). No data should be reported beyond the range of calibration of the methodology. Appropriate quality control samples and experiments must be included to verify that interferences are not present with the analytes of interest, or, if they are, that they be removed or accommodated. 

Control samples should have a high degree of similarity to the actual samples analyzed otherwise, one cannot draw reliable conclusions on the measurement system s performance. Control samples must be so homogeneous and stable that individual increments measured at various times will have less variability than the measurement process itself. Quality Control samples are prepared by adding known amounts of analytes to blank specimens. They can be purchased as certified reference material (CRM) or may be prepared in-house. In the latter case, sufficient quantities should be prepared to allow the same samples to be used over a longer period of time. Their stability over time should be proven and their accuracy verified, preferably through interlaboratory tests or by other analysis methods. 

No final answer can be given to this question, for similar cases are also known in wet chemistry (for example, the Pack Analyzer ACA of DuPont de Nemours). Here, too, the apparatus or method is calibrated once for every batch and is rechecked daily or at regular intervals by means of the quality control sample. The system of dry chemistry can be viewed under the same aspect. The Ektachem system is known to be stable for more than 6 months, so that the apparatus or method need not be readjusted during this period but only supervised via quality control checks. The problem of calibration does not arise with Reflotron, since all the requisite data (calibration data) are stored on the reverse of the test slides. No data, however, are available on long-term studies of stability. The FDA has prescribed a 7-day or 30-day calibration rhythm for the Seralyzer system depending on the analyte to be analysed. 

Typically, fresh calibration curves in control matrix are prepared for each day of analysis. Alternatively, calibration standards may be prepared in bulk, sub-divided and stored under conditions typical for sample storage for as long as storage stability has been established. Quality control samples are typically prepared in bulk. After preparation the QC pool is sub-divided and stored under conditions typical for study sample storage. As a result of stability concerns or unusual matrix limitations, QC samples may be prepared fresh from spiking solutions (individually or in bulk). In any event the identity, preparation dates and storage location and conditions used for calibration standards and QCs should be included in the report. 

For an accurate quality check. Quality Control (QC) samples are interspersed among actual samples at intervals determined by the total number of samples and the precision and reproducibility of the method. The control sample frequency will depend mainly on the known stability of the measurement process, a stable proce.ss requiring only occasional monitoring. Huber [10] recommends that 5 % of sample throughput should consist of quality control samples for routine analysis and 20-50% for more complex procedures. 

Based on these results, UHPLC coupled to high-resolution MS seems to be the best choice for metabolomics, and the workflow diagram of a typical MS-based metabolite profiling study is presented in Figure 4.8. However, it is also important to check whether the retention time stability and mass accuracy are sufficient because they can critically influence the number of detected features and the data treatment method. This topic was widely discussed in several recent papers (99, 110). One example reported that the shift in the retention time and the mass shift were only 0.03 min and less than 4 ppm, respectively, after 600 injections of a pooled quality control sample over a 5 day period (102). Similar results were also obtained in another study (101), in which the retention times and mass shifts were estimated to be 0.03 min and less than 5 ppm, respectively. Finally, it was discovered that the first few injections on the UHPLC system were not representative and should be discarded (99). Therefore, based on the assessment of the QC samples, UHPLC-MS provides a powerful and repeatable method for the global metabolomic analysis of biological samples (99, 110). 

Residue study protocols typically either include quality specifications for analytical procedures or refer to a written analytical method that includes such specifications. The protocol for an LSMBS should also include analytical quality specifications, either directly or by reference to a method. Analytical specifications usually include minimum and maximum recovery of analyte from fortified control samples, minimum number of such fortifications per set of samples, minimum linearity in calibration, minimum stability of response to injection of calibration solutions, and limits of quantitation and of detection. 

The design of an assay is, in large measure, prospective quality assurance. The factors that are likely to affect the results of the assay must be defined and controlled to the greatest extent possible. Once the general outlines of an assay have been established, key features should be examined, including optimization of sample preparation, sample stability, choice of standards, assay range, assay repeatability, optimization of separation, and optimization of detection. 

GFAAS end analysis of Pb in blood was critically discussed in a review, including methods of introducing the sample into the furnace, matrix interferences and ways of improving the precision of the method, such as use of a stabilized temperature platform40. An evaluation program was carried out for quality control materials and proficiency for... 

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... 

Independent of existing intra-lot variability, a sample size of six dosage units is generally recognized to suffice the needs of quality control (QC). In very early development less than six specimens may be used to create data, but as soon as possible tests should be run with at least n = 6. It is advisable to create statistically valid and sound data for manufacturing prototypes even at very early phases of development, in order to be able to identify formulations/batches with unwanted dissolution behavior. In the early phases of a drug product s development, formulations may not be of acceptable stability. This means that stability phenomena may mask... 

Stability of Standard and Sample Solutions. Appropriate stability of the standard and sample solutions will allow flexibility of the method to be used in a quality control laboratory. For example, 4-day stability of the standard and sample solutions will allow investigation if problems arise during a weekend HPLC run. 

The analysis of quality control (QC) samples with the construction of quality control charts has been suggested as another way of performing PQ. Control samples with known amounts are interdispersed among actual samples at intervals determined by the total number of samples, the stability of the system, and the precision specified. The advantage of this procedure is that the system performance is measured more or less continuously under conditions that are very close to the actual application. 

Lyphochek quantitative urine control includes a normal and an abnormal level of ALA. For PBG quality control, we recommend using a positive patient urine sample stabilized with 1% sodium azide and kept in aliquots at -20°C. 

Tensile properties are used in the evaluation of batches of material as well as in determining the aging effects on polyurethane. Currently, the time taken for the preparation and stabilization of the samples does not make this test ideal for a batch-to-batch real-time quality control tool. Testing is normally carried out to one of the following standards ... 

---