Quantitative limitations

The U.S. FDA monitors foods for half of the approximately 300 pesticides having official EPA tolerances as weU as a number of other pesticides that have no official tolerances. Multiresidue methods, most of which are based on chromatography protocols, are employed (7). Not aU pesticides are monitored on aU foods and sampling (qv) is purposely biased to catch possible problems. The overaU iacidence of iUegal pesticide residue is, however, quite smaU 1% for domestic surveiUance samples and 3% for imported foods. The methods employed can usuaUy quantify residues present at 0.01 ppm. Quantitation limits range from 0.005 to 1 ppm. 

A study was conducted to measure the concentration of D-fenfluramine HCl (desired product) and L-fenfluramine HCl (enantiomeric impurity) in the final pharmaceutical product, in the possible presence of its isomeric variants (57). Sensitivity, stabiUty, and specificity were enhanced by derivatizing the analyte with 3,5-dinitrophenylisocyanate using a Pirkle chiral recognition approach. Analysis of the caUbration curve data and quaUty assurance samples showed an overall assay precision of 1.78 and 2.52%, for D-fenfluramine HCl and L-fenfluramine, with an overall intra-assay precision of 4.75 and 3.67%, respectively. The minimum quantitation limit was 50 ng/mL, having a minimum signal-to-noise ratio of 10, with relative standard deviations of 2.39 and 3.62% for D-fenfluramine and L-fenfluramine. 

The method was validated in accordance to the guidelines of the international conference on harmonization (ICH). Data with respect to accuracy, within- and between run precision, recovery, detection and quantitation limits were reported and found to be within the accepted international criteria. Neither endogeneous substances nor the commonly used dmgs were found to interfere with the retention times of the analytes. Standard solutions of the dmg and quality control preparations at high and low level concentrations were demonstrated to be stable at room temperature and/or -20°C for long and short periods of time. 

Regulatory control is governmental imposition of limits on emission from sources. In addition to quantitative limits on emissions from chimneys, vents, and stacks, regulations may limit the quantity or quality of fuel or raw material permitted to be used the design or size of the equipment or process in which it may be used the height of chimneys, vents, or stacks the location of sites from which emissions are or are not permitted or the times when emissions are or are not permitted. Regulations usually also specify acceptable methods of test or measurement. 

The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample, which can be quantitatively determined with suitable precision and accuracy. 

The difference, e.g., 5.0 - 1.4 in the eolumn marked 20 ng/ml, must be attributed to the interpolation error, which in this case is due to the uneer-tainties associated with the four Rodbard parameters. For this type of analysis, the FDA-accepted quantitation limit is given by the lowest ealibration concentration for which CV < 15%, in this case 5 ng/ml the eross indicates... 

A result below the quantitation limit would be given by this example, five, would be substituted, the rule being that option is chosen which makes it harder to prove a hypothesis or lowers the risk of a false statement. 

To solve a quantitative limiting reactant problem, we identify the limiting reactant by working with amounts in moles and the stoichiometric coefficients from the balanced equation. For the ammonia synthesis, if we start with 84.0 g of molecular nitrogen and 24.2 g of molecular hydrogen, what mass of ammonia can be prepared First, convert from... 

The data are also represented in Fig. 39.5a and have been replotted semi-logarithmically in Fig. 39.5b. Least squares linear regression of log Cp with respect to time t has been performed on the first nine data points. The last three points have been discarded as the corresponding concentration values are assumed to be close to the quantitation limit of the detection system and, hence, are endowed with a large relative error. We obtained the values of 1.701 and 0.005117 for the intercept log B and slope Sp, respectively. From these we derive the following pharmacokinetic quantities ... 

Fig. 39.8. (a) Semilogarithmic plot of plasma concentration Cp (pg I" ) versus time t. The straight line is fitted to the later part of the curve (slow 3-phase), with the exception of points that fall below the quantitation limit. TTte intercept B of the fitted line is the extrapolated plasma concentration that would have been obtained at time 0 with an intravenous injection. The slope sp is proportional to the transfer constant of elimination k. (b) Semilogarithmic plot of the residual plasma concentration C (pg r ) versus time t, on an expanded time scale t. The straight line is fitted to the first part of the residual curve (fast a-phase), with the exception of points whose residuals fall below the quantitation limit. The intercept B of the fitted line, is the same as that in panel a. The slope is proportional to the transfer constant of absorption from the extravascular compartment. 

The semilogarithmic plot of the data is given in Fig. 39.8a. On this plot we can readily identify the linear 3-phase of the plasma concentrations between 30 and 240 minutes. The last three points (at 360, 480 and 720 minutes) have been discarded because the corresponding plasma values are supposed to be close to the quantitation limit of the detection system. 

Sensitivity is a measure of the smallest concentration that can be either measured [limit of detection (LOD)] or accurately quantitated [limit of quantitation (LOQ)]. In the USA, the method for measuring LOD or LOQ is left up to the method developer. European requirements for determining LOD and LOQ are very specific the LOD is based on the mean plus three standard deviations for 20 control blank samples, and the LOQ is defined as the lowest concentration giving an acceptable CV. 

The MDL and practical quantitation limit (PQL) should be appropriate for the objectives of the analysis. MDL refers to the minimum concentration of the compound of interest that can be measured and reported with a specified confidence (99% probability) that the concentration is above zero. The registrants must provide or develop an analytical method for water for the parent pesticide and its degradates that has an MDL of 0.01% of the label application rate (calculated as the average concentration in the top six inches of soil), or 0.05 pgL , whichever is lower. PQL refers to the lowest concentration at which the laboratory can confidently quantify the concentration of the compound of interest. The study authors must report all samples with concentrations above the MDL as detections, including those below the PQL in which the concentration cannot be quantified. In addition, the study authors must provide sample equations to demonstrate how the PQL was calculated. 

Method validation is needed to demonstrate the acceptability of the analytical method. A recovery test on a chemical being determined should be performed in order to verify the reliability of the series of analyses. Recovery studies are usually conducted by spiking untreated sediment with the target chemical at the deteetion limit, quantitation limit and in the range of 10-50 times the detection limit. The method is considered acceptable when the recoveries typically are greater than 70%. When the recovery is less than 70%, an improvement in the analytical methods is needed. Where this is not possible for technical reasons, then lower recovery levels may be acceptable provided that method validation has demonstrated that reproducible recoveries are obtained at a lower level of recovery. Analysis is usually done in duplicate or more, and the coefficient of variation (CV) should be less than 10% to ensure that recoveries will be consistently within the range 70-110%. 

Validate routine methods, i.e., define the conditions under which the assay results are meaningful.115 To do that, one must select samples that are truly representative of the product stream. This may be a difficult task when the process is still under development and the product stream variable. The linearity of detector response should be defined over a range much broader than that expected to be encountered. Interference from the sample matrix and bias from analyte loss in preparation or separation often can be inferred from studies of linearity. Explicit detection or quantitation limits should be established. The precision (run-to-run repeatability) and accuracy (comparison with known standards) can be estimated with standards. Sample stability should be explored and storage conditions defined. 

The version 1.0 bDNA assay was compared with the Monitor and NASB A HIV-1 RNA assays in three clinical evaluations (Coste et al., 1996 Revets et al., 1996 Schuurman et al., 1996). Coste et al. (1996) found that the sensitivity of the bDNA assay was lower (68.3%) than that of both the Monitor (93.3%) and NASBA (100%) assays for detection of HTV-1 RNA among 60 plasma specimens. When results with specimens for which the RNA levels were higher than the lower quantitation limit of each method were analyzed, the mean levels by Monitor, bDNA, and NASBA were 5.38 0.52,5.03 0.55, and 5.39 0.53 log10 copies/ml, re-... 

Second, it is possible to establish an agreement that sets quantitative limits of emissions and allocates emission permits to firms (or States) but allows to trade among countries, in order to minimize abatement costs. The starting allocation of permits can be set through either an auction or a grandfather allocation. Under an auction, government (or the international community) sells the emission permits, whereas under the grandfather rule, the allocation of emission permits is based on historical records. 

In the global-warming context, quantitative limits set targets on the time path of GHG emissions of different countries. Countries then can administer these limits in their own fashion, and the mechanism may allow transfer of emission allowances among countries, as is the case under the Kyoto Protocol. 

The limit of quantification (LQ, limit of determination, quantitation limit), Xiq, being the lowest content which can quantitatively be determined with a given precision (mostly expressed by the relative uncertainty of measurement)... 

Column Mobile phase Detection Analyte(s) and sample Extraction and cleanup Detection limit (DL), quantitation limit (QL) and recovery (Rec) Reference... 

Dean et al. [93] used a high performance liquid chromatographic method for the simultaneous determination of primaquine and carboxyprimaquine in plasma with electrochemical detection. After the addition of the internal standard, plasma was deproteinized by the addition of acetonitrile. Nitrogen-dried supernatants, resuspended in mobile phase were analyzed on a C8 reversed-phase column. Limits of detection for primaquine and carboxyprimaquine were 2 and 5 ng/mL with quantitation limits of 5 and 20 ng/mL, respectively. The assay sensitivity and specificity are sufficient to permit quantitation of the drug in plasma for pharmacokinetics following low dose (30 mg, base) oral administration of primaquine, typically used in the treatment of malaria and P. carinii pneumonia. 

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