Analytical methods limits of detection

The lower end of the working range is limited by the detection capabihties of the analytical method. Limit of detection and limit of quantification (sometimes also called limit of quantitation or limit of determination) describe these capabilities of the method. 

Because acceptable recoveries were obtained at O.Olmgkg", the method LOQ is 0.01 mg kg for flucarbazone-sodium and O.Olmgkg" for Af-desmethyl flucarbazone in all wheat samples. Linearity curves in both solvent and matrix blanks were mn from 0.005 to 0.100 mg kg . Because 0.005 mg kg of each analyte was reliably detected, the method limit of detection (LOD) was 0.005 mg kg in all wheat samples. 

Lemire et al. (32) reported a quantitative method for the determination of IV-ethyl- and A-methyldi-ethanolamine, the hydrolysis products of HN-1 and HN-2, in urine using LC/ESI/MS/MS on a triple sector quadrupole instrument. The analytes were concentrated from urine by SPE on a strong cation exchanger. In order to obtain good peak shapes, 73% 3mM ammonium hydroxide (pH 10.5) - 27 % methanol was used as the mobile phase for LC. Isotope dilution ([13C]4-/V-Me and N-Et diethanolamines) was used to compensate for inherent variabilities. Detection was by MRM, monitoring the transition MH+ —> [MH-H20]+ for each analyte. The limits of detection were 0.4 ng/ml for V-ethyldiethanolaminc and 1 ng/ml for N-methyldiethanolamine. An interferent was present in urine with similar retention time and nominal mass characteristics as /V-mclhyldiclhanolaminc. 

The most important criterion for selecting an analytical method is whether the technique is sufficiently sensitive to measure the amount of radionuclide present in the sample. This is a very different problem when considered from the viewpoint of analytical chemists who use radiometric methods and those who use non-radiometric methods. Limits of detection in radiometric methods can be as low as lO" Bq, although 1 mBq is a more generally attainable detection limit. For non-radiometric methods, the detection limit is expressed in terms of mass and the relationship between radio-metric and non-radiometric limits of detection will depend upon the half-life of the radionuclide of interest. 

Sensitivity. The sampling and analytical method together should ideally have a limit of detection much less than the exposure limit. Less sensitive methods are stiU usable, however, as long as the limit is easily within the range of the method. 

An analytical method vahdation study should include demonstration of the accuracy, precision, specificity, limits of detection and quantitation, linearity, range, and interferences. Additionally, peak resolution, peak tailing, and analyte recovery are important, especially in the case of chromatographic methods (37,38). 

Method Transfer. Method transfer involves the implementation of a method developed at another laboratory. Typically the method is prepared in an analytical R D department and then transferred to quahty control at the plant. Method transfer demonstrates that the test method, as mn at the plant, provides results equivalent to that reported in R D. A vaUdated method containing documentation eases the transfer process by providing the recipient lab with detailed method instmctions, accuracy and precision, limits of detection, quantitation, and linearity. 

A multiresidue analytical method based on sohd-phase extraction enrichment combined with ce has been reported to isolate, recover, and quantitate three sulfonylurea herbicides (chlorsulfuron, chlorimuron, and metasulfuron) from soil samples (105). Optimi2ation for ce separation was achieved using an overlapping resolution map scheme. The recovery of each herbicide was >80% and the limit of detection was 10 ppb (see Soil chemistry of pesticides). 

Biopolymers are employed in many immunological techniques, including the analysis of food, clinical samples, pesticides, and in other areas of analytical chemistry. Immunoassays (qv) are specific, sensitive, relatively easy to perform, and usually inexpensive. For repetitive analyses, immunoassays compare very favorably with many conventional methods in terms of both sensitivity and limits of detection. 

Analytical techniques (including method, accuracy, precision, reproducibility, robustness, limits of detection). 

Limit of detection (LOD) The smallest amount of contaminant that can be reliably detected by a particular analytical method. 

By using modem production methods it is possible to reduce the amounts of 1,4-dioxane to a level that is barely detectable with the best current analytical methods. Free ethylene oxide is now below detectable levels. Furthermore, volatile and nonvolatile nitrosamines ( NDELA ) both seem to be below detection limits of ppb in the alkanolamide-based sulfosuccinates. A good overview of modern analytical methods for the detection of 1,4-dioxane and ethylene oxide as well as nitrosamines and formaldehyde is given in Ref. 60. 

The attributes required of a method usually include good sensitivity, low hmits of detection, and selectivity. It must be recognized that while low limits of detection will usually require good sensitivity, the latter, in itself, does not guarantee low limits of detection since these are often determined by the levels of interfering materials present and not the absolnte sensitivity of the technique. Low limits of detection allow the analyte to be determined at levels at or below those considered to be harmful or prescribed by legislation or at which it is found in a particular... 

GC/MS has been employed by Demeter et al. (1978) to quantitatively detect low-ppb levels of a- and P-endosulfan in human serum, urine, and liver. This technique could not separate a- and P-isomers, and limited sensitivity confined its use to toxicological analysis following exposures to high levels of endosulfan. More recently, Le Bel and Williams (1986) and Williams et al. (1988) employed GC/MS to confirm qualitatively the presence of a-endosulfan in adipose tissue previously analyzed quantitatively by GC/ECD. These studies indicate that GC/MS is not as sensitive as GC/ECD. Mariani et al. (1995) have used GC in conjunction with negative ion chemical ionization mass spectrometry to determine alpha- and beta-endosulfan in plasma and brain samples with limits of detection reported to be 5 ppb in each matrix. Details of commonly used analytical methods for several types of biological media are presented in Table 6-1. 

Adequate sensitivity should be demonstrated and estimates of the limit of detection (LOD) and the limit of quantitation (LOQ) should be provided. The slope of the calibration line may indicate the ability of the method to distinguish the tme analyte concentration. The LOD of a method is the lowest analyte concentration that produces a reproducible response detectable above the noise level of the system. The LOQ is the lowest level of analyte that can be accurately and precisely measured. For a regulatory method, quantitation is limited by the lowest calibration standard. The techniques for these estimations should be described. 

The limit of detection (LOD) is an important criterion of the efficiency of an analytical method. It is characterized by the smallest value of the concentration of a compound in the analytical sample. The detectable amount of anilide compounds is in the range 0.01-0.5 ng by GC and 0.1 ng by HPLC. The limit of quantitation (LOQ) ranges from 0.005 to 0.01 mg kg for vegetables, fruits and crops. The recoveries from untreated plant matrices with fortification levels between 10 and 50 times the LOD and the LOQ are 70-120%. The relative standard deviation (RSD) at 10-50 times the level of the LOD and LOQ are <10 % and <20%, respectively. 

The MDCs are estimated from an S/N of the diphenyl ether peaks of at least of 3 in the recovery test. With fortification levels between 0.2 and 0.5mgkg recoveries of bifenox from brown rice matrices ranged from 85 to 102% with the limit of detection (LOD) and limit of quantitation (LOQ) being 0.010 mg kg according to the analytical method of the Notification of the Ministry of the Environment, Japan. By the residue analysis method described in Section 2.2.2(3), recoveries of chlornitrofen and CNP-NH2 from brown rice and vegetables with fortification levels of 0.04-0.10 mg kg ranged from 82 to 98%. The LOD for each sample was 0.005 mg kg for chlornitrofen and CNP-NH2. ... 

Method validation determined the limit of detection (LOD) to be 1 ngL (ppt) for isoxaflutole, 1 ngL for RPA 202248 and 3 ngL for RPA 203328. However, after experience with a number of surface waters with high levels of matrix components, the method LOD was increased to 3 ng L for all three analytes. RPA 202248 also proved to be particularly sticky and prone to carry over. Over time, this produced abackground level, which also prevented determinations below the 3ngL method LOD. 

Third, the bulk of the items in Table 1 address method performance. These requirements must be satisfied on a substrate-by-substrate basis to address substrate-specific interferences. As discussed above, interferences are best dealt with by application of conventional sample preparation techniques use of blank substrate to account for background interferences is not permitted. The analyst must establish a limit of detection (LOD), the lowest standard concentration that yields a signal that can be differentiated from background, and an LOQ (the reader is referred to Brady for a discussion of different techniques used to determine the LOD for immunoassays). For example, analysis of a variety of corn fractions requires the generation of LOD and LOQ data for each fraction. Procedural recoveries must accompany each analytical set and be based on fresh fortification of substrate prior to extraction. Recovery samples serve to confirm that the extraction and cleanup procedures were conducted correctly for all samples in each set of analyses. Carrying control substrate through the analytical procedure is good practice if practicable. 

Crops, food, and feed. The first recommended method is based on the Dutch Multiresidue Method 2 for A-methylcarbamates, which was originally developed by de Kok et The method has recently been validated by DuPont Crop Protection and Batelle, Geneva Research Centres, for the analysis of methomyl and oxamyl in dry, high-water, high-fat, and high-acid content crops and in various grape processed products. The limit of detection for each analyte is 0.003-0.005 mg kg . ... 

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