Quality control sample types

The analysis of quality control samples is an important activity for laboratories and to make the most of the data, control charts should be used. This chapter has discussed a number of common types of control chart and described how they are set up and interpreted. 

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. 

To monitor the quality of the data from this program, four types of quality control samples (reference, duplicate, replicate, blank) are regularly submitted to the analysts together with routine monthly composite and weekly samples. These quality control samples are submitted blind (i.e., in such a way as to be indistinguishable from the routine samples by the analyst) insofar as this is possible. 

Calibration Standards and Quality Control Samples Documentation to confirm the accurate preparation of the calibration standards and QCs is essential and should include the type and source of matrix, the identity of the reference standard stock solution, the calibration range, concentrations of the individual calibration standards and QCs, regression type and weighting factor (if any), the storage location (e.g., equipment identifiers), and temperature conditions for duration of storage. 

The most common method would be off-line or grab samples, which are taken intermittently and transported to the laboratory for analysis (Figure 9.1(a)). The procedure can be slow and the process may be finished before the results are available. This is more suited to quality control samples taken at the end of the process. Increasingly, samples can be taken at-line (Figure 9.1(b)). These types of samples are also taken intermittently but analysed in an instrument that is very close to the process, i.e. in the plant itself. The next type of sample (on-line samples) are taken from the process (usually automatically) and transferred directly into the analytical instrument for analysis without human intervention (Figure 9.1(c)). Pretreatment of the sample may also be carried out automatically as part of the assay. 

Much less data are available on the adsorption of elements onto surfaces from blood or urine samples. Stoeppler (1980) did not detect any loss of added Ni from urine samples onto polyethene container walls. Concentrations of nickel or chromium in urine samples, spiked with small concentrations of the metals and stored for 6 months at 4°C did not show a decrease (Kiilunen et al.. 1987). The lUPAC reference method for nickel in urine calls for acidification of urine quality control samples with nitric acid and storage in polypropene tubes with a screw-cap at -20°C (Brown et al., 1981). No adsorption of cadmium onto container walls (type not specified) was seen from urine acidified to pH < 2 (Stoeppler and Brandt, 1980). 

Table 13.2 suggests the types and number of radiation detectors needed for the laboratory. The first column lists the equipment to process 1000 samples per month. For radioanalytical chemistry laboratories that processes level C and D samples, count times per sample are in the 50-1,000 min range. If higher-level A and B samples are processed, the brief count times require fewer detection instruments. The recommended equipment number provides for counting the radiation background, calibration standards and quality control samples as well as the actual samples. 

Before any analytical runs are conducted, the analytic instrument must be calibrated. This is to be done at the beginning of each day on which quality control samples and/or compliance samples are run. Once calibration is established, quality control samples or compliance samples may be run. Regardless of the type of samples run, every fifth sample must be a standard to assure that the calibration is holding. 

The types and amount of quality control used during the field component of a study can vary depending on the data requirements of the stu. At a minimum, field blanks should be used to identify any contamination either through direct contact or airborne exposure of the sample. Other quality control samples to be considered include equipment blanks, if the same sampling equipment is repetitively used, trip blanks (contaminant-free water samples which accompany the field collected samples from the field to the laboratory but are not exposed to the air), and positive control... 

Suppression of analyte signal is a serious problem for any type of mass spectrometric analysis, but it is most serious and most easily observed in quantitative analysis as an unexpected deviation of standard curve points and quality control samples (QCs) from expected values." " Sample clean-up and chromatography are the most effective methods to control suppression. Fast chromatographic techniques are the most prone to exhibit these effects where compounds elute close to the column void in the vicinity of the majority of the sample matrix. Some components of biological matrices, particularly lipophilic compounds that exert the most serious effects in ESI, adhere strongly to C18 columns to such an extent that they can unpredictably elute from a column after several subsequent sample injections. 

Note 9—It is recommended that at least one type of control samde used in 11.1 be representative of the fueKs) regularly tested by the laboratory. The totd vapor pressure measurement process (including operator technique) can be checked periodically by performing this test method on previously prepared samples from one batdi of product, as per procedure describe in 8.1.2. Samples should be stored in an environment suitable for long term storage without sami d radation. Analysis of result(s) from these quality control samples can be carried out using control chart techniques. ... 

Photoelectric-Colorimetric Method. Although the recording spectrophotometer is, for food work at least, a research tool, another instrument, the Hunter multipurpose reflectometer (4), is available and may prove to be applicable to industrial quality control. (The newer Hunter color and color difference meter which eliminates considerable calculation will probably be even more directly applicable. Another make of reflection meter has recently been made available commercially that uses filters similar to those developed by Hunter and can be used to obtain a similar type of data.) This instrument is not a spectrophotometer, for it does not primarily measure the variation of any property of samples with respect to wave length, but certain colorimetric indexes are calculated from separate readings with amber, blue, and green filters, designated A, B, and G, respectively. The most useful indexes in food color work obtainable with this type of instrument have been G, which gives a... 

The identification of sampling requirements involves specifying the sampling design, the sampling method, sample numbers, types, and locations, and the level of sampling quality control. Data quality requirements include precision, accuracy, representativeness, completeness, and comparability. 

There are two uses of chemical standards in chemical analysis. In the first place, they may be used to verify that an instrument works correctly on a day-to-day basis - this is sometimes called System Suitability checking. This type of test does not usually relate to specific samples and is therefore strictly quality assurance rather than quality control. Secondly, the chemical standards are used to calibrate the response of an instrument. The standard may be measured separately from the samples (external standardization) or as part of the samples (internal standardization). This was dealt with in Section 5.3.2. 

This is the simplest type of control chart. It is typically used to monitor day-to-day variation of an analytical process. It does so by monitoring the variation of a quality control (QC) sample or standard when measured by the process. Measurement value is plotted on the v-axis against time or successive measurement on the x-axis. The measurement value on the v-axis may be expressed as an absolute value or as the difference from the target value. The QC sample is a sample typical of the samples usually measured by the analytical process,... 

There is no experimentally established optimum frequency for the distribution of samples. The minimum frequency is about four rounds per year. Tests that are less frequent than this are probably ineffective in reinforcing the need for maintaining quality standards or for following up marginally poor performance. A frequency of one round per month for any particular type of analysis is the maximum that is likely to be effective. Postal circulation of samples and results would usually impose a minimum of two weeks for a round to be completed and it is possible that over-frequent rounds have the effect of discouraging some laboratories from conducting their own routine quality control. The cost of proficiency testing schemes in terms of analysts time, cost of materials and interruptions to other work has also to be considered. 

Quality control material A material that is fully characterized in-house or by a third-party, similar in composition to the types of samples normally examined, stable, homogeneous and available in large quantities so that it can be used over a long period of time for monitoring method performance. 

In the new vision, assay cycle time is dramatically reduced and the criteria used to measure assay acceptability are matched to sample type. Early screening samples may be assayed using simple methods and minimum numbers of standards. Samples from early preclinical PK studies in rats and other species may require additional standards. Finally, for PK studies performed in the lead characterization phase, one might add quality control (QC) samples. One set of rules for non-GLP assays has been codified in a recent publication.16 These rules make it possible to match the assay cycle time with the in-life cycle time in order to minimize the total discovery cycle time. 

Since surfactants are commercially produced by means of large-scale chemical processes, complex mixtures of homologues and isomeric compounds, e.g. non-ionics of the alkylethoxylate type that may differ in length of alkyl as well as polyether chains, can result. The determination and differentiation of the products in quality control during production and trade is a somewhat easier task. However, more difficulties arise in the analysis of the compounds of these mixtures and formulations in environmental samples. 

Another RP-HPLC technique has been applied for the determination of synthetic food dyes in soft drinks with a minimal clean-up. Separation of dyes was obtained in an ODS column (150 x 4 mm i.d. particle size 5 pm). Solvents A and B were methanol and 40 mM aqueous ammonium acetate (pH = 5), respectively. Gradient conditions were 0-3 min, 10 per cent A 3-5 min, to 25 per cent A 5-8 min, 25 per cent A 8-18 min, to 75 per cent A 18-20 min, 75 per cent A. The flow rate was 1 ml/min and dyes were detected at 414 nm. The separation of synthetic dyes achieved by the method is shown in Fig. 3.35. The concentrations of dyes found in commercial samples are compiled in Table 3.21. The quantification limit depended markedly on the type of dye, being the highest for E-104 (4.0 mg/1) and the lowest for E-102 and E-110 (1.0 mg/1). The detection limit ranged from 0.3 mg/1 (E-102 and E-110) to 1.0 mg/ml (E-104 and E-124). It was suggested that the method can be applied for the screening of food colourants in quality control laboratories [113]. 

The strict regulations of the pharmaceutical industry have a significant effect on the quality control of final products, demanding the use of reliable and fast analytical methods. The capacity that the technique has for the simultaneous determination of several APIs with no need of, or with minimum, sample preparation has considerably increased its application in pharmaceutical analytical control. The main limitation of NIR is the relatively low sensitivity that limits the determination of APIs in preparations when their concentration is less than 0.1%. Nevertheless, instrumental improvements allow the determination below this limit depending on the nature of the analyte and the matrix, with comparable errors to the ones obtained with other instrumental techniques. The reference list presents an ample variety of analytical methodologies, types of samples, nature of analyte and calibration models. A detailed treatment of each one is beyond the scope of... 

The rules for level I (screening) assays are shown in Table 13.1. An example of the type of samples where a level I assay could be used is the CARRS samples [85] that can be used for screening NCEs using a rat PK model [vide supra). The concept behind this assay is that it should use a small number of standards and a simple linear extrapolation. For level II assays (see Table 13.2) that might be used for discovery PK studies in preclinical species, a complete standard curve is required. In this case a complete standard curve is defined as 10-15 standards in duplicate assayed with at least five standards used in the final calibration curve. Neither level I nor level II assays require the use of quality control (QC) standards. When a compound is in the lead qualification stage, then a level III assay would be required. As shown in Table 13.3, the main distinction for level III assays is that they are required to include at least six QC standards. As described in Tables 13.1-13.3, these rules show the requirements for how an assay should be set up before the samples are assayed and then these rules describe the acceptance criteria for the assays after they have been performed. 

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