Laboratory control limits

Analytical laboratories establish the accuracy of the performed methods through the preparation and analysis of laboratory control samples, the same samples that are used for the determination of laboratory precision. Based on a statistical evaluation of the recoveries from these interference-free matrices, laboratories derive the recovery acceptance criteria, called laboratory control limits. 

To establish reasonable acceptance criteria for accuracy during planning, we should obtain statistical laboratory control limits from the laboratory that will perform analysis for the project samples. We should also be aware of matrix interferences in environmental samples that may reduce the accuracy of analysis. As part of QC procedures, to estimate the effects of matrix interference on accuracy, laboratories perform the accuracy determinations on environmental samples, known as matrix spike (MS) and matrix spike duplicate (MSD). These fortified samples enable the laboratory to detect the presence of interferences in the analyzed matrices and to estimate their effect on the accuracy of sample analysis. (In the absence of matrix interferences, an additional benefit from MS/MSD analysis is an extra measure of analytical precision calculated as the RPD between the two recoveries.)... 

Another tool that enables us to evaluate analytical accuracy of organic analyses is surrogate standards. These are compounds that do not naturally occur in the environment and that are similar in chemical nature and behavior to target analytes. In organic compound analysis, known amounts of surrogate standards are added to each sample prior to extraction. The comparison of surrogate standard recoveries to laboratory control limits permits the laboratory to monitor the efficacy of extraction and to measure the accuracy of analysis for each individual sample. 

Similar to LCS recoveries, surrogate standard recoveries should be monitored by the laboratory and plotted as control charts. The EPA recommends the use of in-house laboratory control limits for surrogate standards recoveries for all organic compound analyses (EPA, 1996a). The exception is the CLP SOW, which specifies these limits for soil and water analysis. Unless affected by matrix interferences, surrogate standard recoveries normally have relatively narrow control limits, 65-135 percent for most organic compound analysis. (Many laboratories, however, default to arbitrary limits of 50-150 percent for GC analyses, instead of using statistical control limits.)... 

The EPA recommends that advisory recovery acceptance criteria of 70-130 percent be used until laboratory control limits become available (EPA, 1996a) however, many laboratories use arbitrary limits as data quality acceptance criteria. The arbitrary selection of acceptance criteria for accuracy and precision is a harmful practice on the part of the laboratory and the data user. Arbitrarily criteria that are too narrow lead to unnecessary data rejection criteria that are too wide damage data... 

Example 5.4 Use acceptance criteria based on laboratory control limits... 

The SAP establishes the advisory accuracy acceptance criteria for EPA Method 8081 of 70-130 percent. The laboratory control limits for accuracy exceed the SAP specification as follows ... 

Laboratory control limits or accuracy as percent recovery 26-120... 

GC/MS methods are the only published methods that include the surrogate standard recovery limit guidance. Similar to LCS, acceptance criteria for surrogate standard recoveries of all other organic analysis methods are the laboratory control limits. The limits for internal standard recovery in GC/MS analysis are specified by the method and cannot be changed by the laboratory. Acceptance criteria for matrix interference detection techniques in trace element analyses, discussed in Chapter 4.4.4.5, are also specified in the analytical methods. 

The laboratory control limits of the BFB surrogate standard in EPA Method 8021 are 56 to 143 percent. The chemist may use the following rationale for qualifying individual sample data with the surrogate standard recoveries outside these limits ... 

Internal QC results should be plotted or charted in a manner which describes sample recovery and laboratory control limits. 

Control limits for a properly working instrument Control limits for a properly standardized instrument Control limits for a correct set of test samples Control limits for duplicate reference values from another laboratory Control limits for agreement between NIRS analysis values and reference method values... 

Control limits for agreement of reference method values between two laboratories Control limits for agreement of NIRS analysis values between two standardized instruments of different models... 

In a micronucleus assay using male B6C3Fj mice dosed with 0, 250, 500, or 1,000 mg/kg diisopropyl methylphosphonate, a small but significant increase in micronuclei were observed at mid- and high-dose levels (DOD 1991a). However, the maximum response was found to be within the laboratory historical control limits. The assay was repeated and the increase in micronuclei was not observed, therefore, it is believed that diisopropyl methylphosphonate did not cause micronuclei induction in this experiment. Diisopropyl methylphosphonate was also negative for the induction of micronuclei in the rat bone marrow after administration of up to 800 mg/kg (DOD 1991b). 

SACHEM Inc. of Cleburne, Texas, manufactures various concentrations of tetramethylammo-nium hydroxide (TMAH) solutions to meet customer specifications. To ensure consistent performance, electronic industry requires very narrow concentration specifications for the solutions. In SACHEM s quality control laboratory, standardized acids such as HC1 or H2S04 are used as titrants for the TMAH solutions to check their concentrations. The performance of the assay titration is controlled by daily analysis of internal reference standards (IRSs). If the IRS results are within controlled limits, then the assay results of a product can be reported. If not, the results cannot be reported until the root cause is uncovered and eliminated. Safety glasses and gloves are worn while performing this work in the laboratory. 

The third candidate showed few malformed larvae in FETAX at concentrations which also caused mortality (10-15%), i.e., two larvae at 6 mg/L, one at 9 mg/L, and two at 12 mg/L. The solubility limit was 12 mg/L. Apart from the absence of one eye at 9 mg/L (malformation never observed in the laboratory control data from 1999), the other four larvae presented malformations known to occur spontaneously in Xenopus larvae (incidences between 1.2 and 1.4% from 2008 to 2010 Fig. 2). In mammalian studies, other candidates with the same pharmacological activity had been found to cause cardiovascular malformations. The embryo-fetal toxicity study in rabbits with this compound revealed a similar teratogenic potential (Table 3). 

Since chemical reactions are accelerated by temperature increases, the recommendation is to store materials at the highest possible temperature consistent with practical limits—i.e.y 165°F., for the longest possible storage period. Storage data generated for liquid and slurry propellants are of two types (1) laboratory controlled experiments, and (2) field tests in hermetically sealed containers. The laboratory experiments provide for rapid and convenient determinations and are used primarily for comparing one propellant with another or for comparing the relative... 

The qualification trials using (10 x size) pilot-laboratory batches have been completed, in which the critical processing steps and process variables have been identified, and the provisional operational control limits for each critical test parameter have been provided... 

When conducting an inspection, several target areas must be evaluated. Control limits or "charts" are helpful and should be established by plotting the defined limits of acceptable quality control. These charts are important tools for assessing laboratory precision, accuracy, and reproducibility. They can be based on a curve established from the high, mid, and low concentrations of a standard analyte. Either the mid level or the average of the three concentrations then becomes the mid-line for the control chart. Acceptable levels of fluctuation for routine mid-level standards,... 

An example of a recovery control chart is shown in Figure 4.7. The mean recovery of individual measurements is represented by the centreline. The upper warning limit (UWL) and the lower warning limit (LWL) are calculated as plus/minus two standard deviations (mean recovery + 2s) and correspond to a statistical confidence interval of 95 percent. The upper control limit (UCL) and the lower control limit (LCL) are calculated as plus/minus three standard deviations (mean recovery 3s), and represent a statistical confidence interval of 99 percent. Control limits vary from laboratory to laboratory as they depend on the analytical procedure and the skill of the analysts. 

The EPA recommends that the control limits of 70-130 percent be used as interim acceptance criteria until the laboratory develops its own limits (EPA, 1996a). In reality, not every laboratory evaluates their analytical precision and accuracy statistically many rely on the EPA guidance or choose control limits arbitrarily. The typical arbitrary control limits are 50-150 percent these limits are sufficiently wide to encompass the recoveries of most organic analytes. As a rule, the control limits of 65-135 percent reflect the typical laboratory accuracy for most organic analytes for metals these limits are 75-125 percent. The arbitrary control limits do not reflect the actual laboratory performance and their routine use is an unacceptable laboratory... 

Due to poor laboratory technique, statistically determined limits may be inadequately wide. For example, recovery limits of zero to 200 percent are not acceptable for any analyte, even if determined statistically they indicate only a poor quality of laboratory work. Such control limits should not satisfy a data user who is concerned with data quality. 

For GC/MS analyses, some laboratories use surrogate standard recovery limits from outdated versions of EPA Methods 8260 and 8270. These recovery limits, shown in Example 4.18, are fairly close to the statistically derived control limits at most laboratories and can be safely used in the evaluation of data quality. The surrogate... 

Obtain control limits from the laboratory that will be providing analytical services to the project and include them in the SAP. 

The surrogate standard recoveries for some samples may be outside the control limits due to sample dilutions or matrix interferences. Such samples are usually clearly identified in the Case Narrative or in the laboratory reports, and their data are not qualified. For example, if a surrogate standard recovery is below 10 percent due to dilution, the result will not be rejected and will not be qualified as an estimated value. The chemist, however, may request from the laboratory the raw data for this sample in order to verify whether the dilution was justified and the interferences were truly present. 

LCL LCS LCSD lower control limit laboratory control sample laboratory control sample duplicate... 

In the routine operation of clinical laboratories worldwide, the performance of analytical methods is routinely monitored by analyzing specimens whose concentrations are known followed by comparing the observed values with the known values. The known values are usually represented by an interval of acceptable values, or upper and lower limits for control (control limits). When the observed values fall within the control hmits, the analyst is assured that the analytical method is functioning properly When the observed values fall outside the control limits, the analyst should be alerted to the possibility of problems in the analytical determination. A number of books are available that discuss the... 

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